Introduction

Mutagens are substances that induce DNA damage and alterations in the DNA sequence. Organisms effectively restore damaged DNA, but complications occur when the damage is not repaired before the cell duplicates (Minamoto et al. 1999). When the life system undergoes mutagenesis, mutagenic substances in the environment have the potential to generate physiological, biochemical, and genetic modifications in all species. Environmental contamination is gaining noteworthy consciousness due to various anthropogenic, natural, and human sources such as volcanic eruptions, inefficient combustion of fossil fuels, oil spills, industrial emissions, process of smelting, incineration, coal scorching, and outpouring from motor vehicles; heavy metals discharged into the environment combined with other environmental stresses have adverse impacts on human and aquatic life (Lu et al. 2021; Wu et al. 2015; Mouchet et al. 2006; Iwegbue et al. 2016; Wang et al. 2004; Wang et al. 2018). Recent investigations reveals that chemical mutagens observed in the environment may cause alterations at both genomic and proteomic levels. Chemical mutagens (cigarette smoke, dietary contaminants, mycotoxin aflatoxin B1, DNA alkylating agents) and physical mutagens (X-rays, UV irradiation, asbestos, radon, infectious pathogens like bacteria and viruses, such as Helicobacter pylori, human papilloma virus, and human hepatitis B and C viruses), as well as lifestyle factors (sunlight exposure), are recognized as critical environmental factors that lead to the development of multiple diseases as shown in Figs. 1, 2, and 3 as reported by a group of researchers (Li et al. 2020; Foster et al. 1983; Hsu et al. 1991). Physical mutagens like ultraviolet (UV) radiation begin a chemical bonding process connecting two substances nearby bases of pyrimidine (CC, TC, CT, and TT) to create dimers of pyrimidine that cause DNA damage. In contrast, ionizing radiation primarily influences the hematopoietic characteristics observed in animals and humans (Rozgaj et al. 1999; Taqi et al. 2018). Chemical mutagens such as dimethyl sulfate (DMS), bisphenol A (BPA), polycyclic aromatic hydrocarbons (PAHs), and 5-chlorocytosine (5ClC) chemical proved hazardous to humans, and generate ROS, creating mutations, chromosomal abnormalities, carcinogenicity, genotoxicity, and distinct genetic changes that have been associated with a broad range of acute and chronic health effects in humans (Zhu et al. 2015; Grimalt et al. 2004; Pribylova et al. 2012; Nekhavhambe et al. 2014). Various heavy metals toxicants such as Cr, Pb, Hg, Cd, As, and Al induced DNA damage with the cell and responsible for generation of neurological disorders in humans. UV-related CT and CCTT conversion, GT modifications produced by dietary aflatoxin B1 exposure, GT and GC mutations linked with tobacco-derived carcinogens, and AT and TA modifications linked with vinyl chloride exposure are also instances of hallmark mutations. The discovery of so-called signature mutations has given evidence linking certain environmental variables to the mutation spectrum associated with tumorigenesis (Hsu et al. 1991; Foster et al. 1983; Denissenko et al. 1996; Spruck et al. 1993). Food also carries mutagens ranging from heterocyclic amines created by barbecuing meats to aflatoxin generated by certain fungal diseases of cereals and peanuts (Rosette and Karin 1996). Exogenous mutagens may also be observed at the workplace and home. In the year 1775, the first report of occupational cancer caused by mutagens in the workplace was observed among males who worked as chimney sweeps that release polycyclic aromatic hydrocarbons known as DNA-damaging agents. Over time, the extended exposure of hydrocarbons caused damaging of DNA and successive mutations, which triggered the emergence of cancer in the scrotum (Palmer and Paulson 1997). Human feces include a family of carcinogenic chemicals called as fecapentaenes, and the foremost type of fecapentaenes are fecapentaene-14 as well as fecapentaene-12. These fecapentaenes are lipid-dissolvable, straight-acting frameshift and base pair mutagens seem to be produced by gut bacteria. Escalated exchanges of sister chromatid, oxidative destruction, and mutagenesis of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) are also caused by fecapentaene-12. Salts of bile were shown to increase overall capability of fecapentaenes-14 as well as -12 to activate repair of DNA in the bacteria and highlight the significance of high-fat, low-fiber diets for colon cancer development (Schrader and Cooke 2003). This review discusses the molecular mechanism of physical mutagens, chemical mutagens, and several heavy metals involved in DNA damage, carcinogenesis, chromosomal abnormalities, and oxidative stress, which lead to complicated ailments and influencing human health. Biological tests for mutagen detection are essential; hence, we also elaborated several methods (Ames test and Mutatox test) to evaluate mutagenic factors in the environment.

Fig. 1
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Classification and mechanism of environmental mutagens impacting human health

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Fig. 2
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Shows the molecular mechanisms of physical mutagens in environment

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Fig. 3
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Shows the molecular mechanisms of chemical mutagens in environment

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Molecular mechanisms of mutagens in environment impacting human health

Physical mutagens (UV rays, X-rays, gamma rays)

Sunlight and UV rays

Molecular mechanisms of physical mutagens in the environment are shown in Fig. 2, the absorption of sunlight directly causes DNA damage, and ultraviolet radiation (UVR) may be an initial genotoxic factor in the environment. Ultraviolet radiation (UVR) exhibits varied effects impacting human health, as explained in Table 1, and it can cause mutagenic DNA damage in the skin. The induction of DNA damage by UV radiation from the sun is an important event in the development of skin malignancies. UV radiation (UVR) is a key environmental stressor for the skin. UVR is made up of three wavelengths: UV-C (200–280 nm), UV-B (280–315 nm), and UV-A (315–400 nm). UV-C and short UV-B (<295 nm) are particularly damaging to cells, although the ozone layer prevents them (Gary and Rochette 2020; Courdavault et al. 2005; Chelladurai et al. 2020). As previously stated, a 10% reduction in total stratospheric ozone concentration enhances UV radiation at 305, 290, and 287 nm by 20, 250, and 500%, respectively (Misra et al. 2002). Sunlight’s mutagenicity and lethality action spectra have two maxima, both in the UV section of the spectrum. The majority of the chemical effects of UVB light on DNA are explained by the conception of dimeric photoproducts involving two neighboring pyrimidine nucleotides (Ravanat et al. 2001). Pyrimidine dimers inhibit most of the DNA polymerases; despite the translesion, DNA polymerases avoid damaging of DNA through incorporation of dAMP contrary to the lesion. Incorporating dAMP opposite to the template T is proper; however, incorporating dAMP opposing to the template C is improper. Although the translesion’s replication permits replication of chromosome to proceed, in pyrimidine dimers, the presence of dAMP opposing template C leads in an AT base pair swap rather than the appropriate GC base pair. Translesion duplication of a -CC- dimer of pyrimidine resulted in base pair changes from GC to AT (Brash 1997). Recent in vitro and in vivo studies revealed p53 gene alterations in UV-exposed skin cells (Nakazawa et al. 1994). Additional investigations have observed that p53 mutation spectra in squamous cell carcinomas of the skin were considered distinct from those seen in internal tumors and remained consistent with the occurrence of CT transitions or CC to TT transitions at sites of dipyrimidine photoproducts, wherein the predominance of CCTT double transitions is thus clearly a sunlight-induced phenomenon. UVC causes skin layer destruction, interfering with chloragogen and epithelial development in intestinal tissues. Furthermore, UV-C induces DNA damage, followed by overexpression of H2AX, a crucial protein implicated in causing DNA repair mechanisms, in a dose-dependent way. Multiple findings illustrate that UVC-induced DNA damage is directly proportional to H2AX expression. The genomic impacts of UV-C light exposure occur through a variety of pathways, the most prominent of which are charge transfer via endogenous chromophores to DNA modifying molecules or direct photon absorption by nitrogenous bases (Sanchez-Navarrete et al. 2020). Apparently, photo-excited configurations of DNA bases that play a role in the predictable outcomes of damage production were illustrated (Markovitsi 2016). The condensation state of the DNA also influences the creation of these pyrimidine dimers. Dipyrimidine photoproducts in sunlight-induced mutagenesis and carcinogenesis, such as cyclobutane pyrimidine dimers (CPD), pyrimidine (6-4), pyrimidone photoproducts (P6-4P), and Dewar photoisomers of P6-4P, are neighboring pyrimidine bases following direct absorption of UVB photons by DNA (Sage et al. 1996). CPDs may develop in both euchromatin and heterochromatin areas, but 6-4PPs can only evolve in euchromatin (Han et al. 2016). Moreover, 5-methylcytosine, loops of G-quadruplex, and telomeres are vulnerable to the generation of CPD. CPDs (cyclobutane pyrimidine dimers) are generated by two covalent connections produced by Frenkel excitons in between carbon atoms C5 and C6 of adjacent bases of nitrogen, resulting in a diastereomeric ring consisting of four components. In the double helix, the cis-syn isomer is more varied than with the trans-syn isomer, whereas the trans-syn isomer predominates in the single-stranded DNA. A charge-transfer connection seen between 5′-end C6 and the 3′-end C4 carbons of nearby pyrimidines produces 6-4PPs, while oxetane and azetidine refinements (unbalanced intermediate) occur when the 3′-end is C or T, accordingly (Markovitsi 2016; Cadet et al. 2012). CPD is a 4-carbon cyclic and rigid ring which is less distortionary than 6-4PP (Taylor et al. 1990; Rastogi et al. 2010; Lee et al. 1998). The intramolecular four electrocyclizations of the pyrimidone ring following photon absorption contribute to just the conversion of 6-4PPs into the isomers of Dewar valence (Perdiz et al. 2010; Douki 2016). A photochemical interaction with an excited state singlet is proposed as the mechanism. The formation of Dewar isomers necessitates the use of two photons: one to stimulate the formation of the 6-4PP and the other to isomerize such DNA lesion. In this case, the second photon is somewhat more expected to be in the UVA range, which is poorly absorbed by ordinary DNA bases but quickly absorbed by 6-4PPs; this is essential for isomerization into the Dewar state. The pyrimidone moiety of 6-4PPs absorbs at around 320 nm: 315 nm for TC 6-4PP and 325 nm for TT 6-4PP. Dewar valence isomers generate an intermediate distortion in structure of DNA when compared to CPDs and 6-4PPs (Lee et al. 1998). In numerous studies employing skin samples, plants, bacteria, and cultured cells, as well as mammals, the 6-4PPs’ isomerization into isomers of Dewar has been developed and evaluated using mass spectrometry and immunological identification (Takeuchi et al. 1998; Pogoda De La Vega et al. 2005; Moeller et al. 2007; Moeller et al. 2010). According to a large-scale study that used microorganisms exposure to natural sunlight, 20% of the 6-4PPs were converted into isomers of Dewar (Maron and Ames 1983). Isomers of Dewar and 6-4PPs are considered to be more harmful than CPDs in terms of pyrimidine dimer mutagenicity. 6-4PPs are principally responsible for TT to TC transitions, whereas Dewar isomers transform TC to TT transitions and CPDs provide C-T transitions (Douki 2016). UVB- and UVA-induced DNA damage preferentially promote C-T transitions in both in vitro and in vivo models (Pfeifer et al. 2005; Kappes et al. 2006; Ikehata et al. 2008). Furthermore, despite the fact that at equimutagenic levels, UVB generates more CPDs than UVA, UVA-induced photoproducts of DNA are possibly more mutagenic than UVB-induced DNA photoproducts. This might be addressed by a less robust arrest of cell cycle, as well as ineffective p95 and p53 activation. As a result, an insufficient cell cycle checkpoint after UVA irradiation may result in the replication of the buildup of mutations and the damaged DNA (Runger et al. 2012). DNA single-strand breaks and double-strand breaks and cross-related DNA linkages can form directly or as a co-product of cellular metabolism after UVA exposure (Dunn et al. 2006; Elvers et al. 2011; Vallerga et al. 2015; Federico et al. 2016). These lesions are very cytotoxic and, if left untreated, may result in chromosomal abnormalities as well as tumorigenic remodeling of keratinocytes. However, UVA radiation’s capacity to effectively trigger double-strand cracks has lately been disproven. This kind of lesion may be an unintended outcome of DNA destruction replication, or it could be caused by UVA-induced bunches of single-strand segments or the repair of nearby oxidized bases in the DNA (Wischermann et al. 2008; Cadet and Douki 2011; Rizzo et al. 2011; Greinert et al. 2012). Immunohistochemical staining of CPDs is now the most extensively used approach for monitoring changes in UV photoproduct levels in human skin. However, since CPDs are very slowly eliminated from the genome, this approach typically requires long periods after irradiation to observe a significant decrease in staining intensity. Furthermore, CPD dilution owing to DNA replication and cell division or death in the skin may result in artifactually lower apparent CPD levels. Finally, methods that use formaldehyde to heal skin tissue may cross-link DNAs to genomic DNA, causing excised UV photoproducts to appear as unrepaired damage (Pouget et al. 2000; Brash et al. 1991; Sawicka et al. 2020).

Table 1 Shows the multiple effects of ultraviolet radiation (UVR) impacting human health
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Ionizing radiations

Ionizing radiation comprises radiation emitted by both naturally occurring and artificial radioactive materials. Hematopoiesis is one of the most radiation-sensitive mechanisms. Ionizing radiation primarily affects the hematopoietic characteristics observed in animals and humans after whole-body irradiation and might be used as a bio-indicator to evaluate ionizing radiation damage (Shafiee et al. 2016; Taqi et al. 2018). Chronic X-ray exposure can result in a significant increase in mean corpuscular volume (MCV), reactive lymphocytes, and a substantial reduction in mean cell hemoglobin concentration (MCHC), WBC, and platelet (PLT) parameters in both male and female (Shafiee et al. 2016; Taqi et al. 2018). Low doses of gamma and X-rays showed high sensitivity of erythrocyte lipid metabolism characteristics. Human leukocyte antigens (HLA) are genes found in major histocompatibility complexes (MHC) that help code for proteins that distinguish self from non-self (Carey et al. 2019). Loss of HLA antigen expression in human lymphoblastoid cell lines may be prompted by 300 R gamma radiation and selection with HLA antiserum. (i) HLA-B8, (ii) HLA-B8, A1, (iii) HLA-B8, A1, DRw3, or (iv) HLA-B8, A1, DRw3 expression is lost (Kavathas et al. 1980).

Chemical mutagens

Environmental pollutants may wreak havoc on genetic material, resulting in a wide range of mutations. Somatic tissue mutations induce cancer, but germinal mutations create a variety of genetic disorders. The frequency, nature (point mutation versus chromosomal change, dominant versus recessive), and strategies that guide a specific mutation in the population will define the influence of germinal mutations on wellbeing (Motulsky 1984). Mutations in somatic cell genetic material may give rise to the neoplasms which are malignant. These carcinogenic implications are mostly limited to the time period between the initial mutation and the diagnosis of clinical cancer. Several environmental toxins have previously been linked to cancer growth and development, including vinyl chloride (liver cancer), benzene (bone marrow malignancies), asbestos (lung and pleural cancer), and others (Doll and Peto 1981). Molecular mechanisms of various chemical mutagens (DMS, BPA, PAHs, 5ClC, biodiesel) are recognized as critical environmental factors that lead to the development of multiple diseases as shown in Fig. 3 (Li et al. 2020; Foster et al. 1983; Hsu et al. 1991).

Dimethyl sulfate

Dimethyl sulfate is a monofunctional alkylating chemical shown hazardous to humans, producing mutations, chromosomal abnormalities, and distinct genetic changes. There are adequate clinical or epidemiological data explicating that dimethyl sulfate is carcinogenic in experimental animals and most likely carcinogenic to humans (Group 2A). It is considered that dimethyl sulfate is a potent genotoxic compound that may directly alkylate DNA both in vitro and in vivo (World Health Organization 1985). DMS is a classic SN2 agent, primarily targeting nitrogen sites in nucleic acids (Hoffmann 1980).

BPA

Humans and animals are exposed to synthetic estrogens that negatively impact both humans and animals (Soto et al. 1997). BPA and its derivatives are xenobiotic estrogens that exist in natural surroundings. BPA is predominantly utilized as a raw chemical in polymer and plastics industries (Fukazawa et al. 2001). Some investigations looked into the genotoxicity of bisphenols at non-cytotoxic levels in the human hepatoma cell line (HepG2) (Fic et al. 2013). BPA is one of the most common endocrine disruptors, and estrogenic substance bisphenol A (BPA, 4,4isopropylidenediphenol) interacts with thyroid hormone receptors in addition to ERs. BPA is the first recognized environmental agent to attach to the TR and influence TH signaling in vitro. BPA inhibits TH-negative feedback on the -TR while leaving the -TR unopposed in reacting to increased T4 in the hippocampus and possibly elsewhere. BPA binds to both the alpha and beta nuclear estrogen receptors (ER) (Maffini et al. 2006; Zoeller et al. 2005). About 40–70% of sporadic spontaneous abortions are associated with chromosomal abnormalities of the conceptus, particularly aneuploidy. High BPA exposure may be linked to recurrent miscarriage, particularly in individuals with ANA (antinuclear antibodies) (Sugiura-Ogasawara et al. 2005). Prenatal exposure to ecologically relevant amounts of BPA caused changes in the reproductive tract and mammary gland visible years after the exposure ceased. Prenatal exposure to environmental BPA levels causes long-term alterations in mammary gland development (Munoz-de-Toro et al. 2005). The cellular transformation being triggered by numerical chromosomal changes in the closer diploid range driven by BPA treatment. Cells were exposed to BPA, which resulted in the production of DNA adducts in a dose-dependent manner. According to several investigations, in cultivated mammalian cells, BPA has cell-transforming and genotoxic consequences, as well as possible carcinogenic activity (Tsutsui et al. 1998). A recent study of BPA was examined for genotoxicity in Swiss albino mice. BPA exhibited genotoxic potential in the bone marrow cells as achromatic lesion and c-mitotic effects (Naik and Vijayalaxmi 2009). BPA has been shown in different species and cell types to alter the topology of the spindle at mitotic and meiotic stage and cytoplasmic microtubule complex, notably human MCL-5 cells and hamster V79 cells. Micronuclei were also found in blood reticulocytes of rats fed nitrite-pretreated BPA but not BPA independently (Pacchierotti et al. 2008). In some studies, the hazardous potential of BPA is due to the development of reactive quinone metabolites and oxidative stress (Fic et al. 2013). BPA may also bind to androgen receptors directly, making it potentially antiandrogenic by inhibiting natural androgen activity (Rochester 2013). The enzymatic metabolism of BPA by cytochrome P450 creates the DNA-reactive quinone form of BPA and generates ROS through enzymatic (H2O2/peroxidase and NADPH/CYP450) and non-enzymatic (peroxynitrite/CO2 and OCl/HOCl) phenoxyl radical production, DNA damage, and cytotoxicity in bone mesenchymal stem cells (hBMSC), hepatocytes, hepatocellular carcinoma (HepG2), neuronal cells (Neuro2a), and spermatogonia (GC-1) (Gassman 2017). Hoxa10, a homeobox gene that regulates uterine organogenesis, is altered due to BPA exposure. BPA has been shown to change global gene expression and interfere with complex cell regulatory networks. BPA induces an adaptive response that modifies the microcellular environment and modifies DNA repair (Gassman et al. 2015).

PAHs

PAHs are hydrophobic environmental contaminants with two or more fused aromatic rings (Zhu et al. 2015; Iwegbue et al. 2016). Anthropogenic sources of polycyclic aromatic hydrocarbons comprise fossil fuel burning, oil spills, and industrial emanation (Iwegbue et al. 2016; Wang et al. 2004; Wang et al. 2018). Natural sources of polycyclic aromatic hydrocarbons incorporate wildfires and volcanic eruptions (Yang et al. 2014; Samburova et al. 2017). Although there are hundreds of PAHs, the United States Environmental Protection Agency (USEPA) has assigned 16 PAHs as precedence carcinogenic and mutagenic substances (Kumar et al. 2012; Liu et al. 2016). Polycyclic aromatic hydrocarbons have been linked with a wide range of acute and chronic health effects, including malformation, mutagenesis, and endocrine system abnormalities (Zhu et al. 2015; Grimalt et al. 2004; Pribylova et al. 2012; Nekhavhambe et al. 2014). Persistent organic pollutants may affect human health via skin contact, ingestion, and inhalation (Yang et al. 2014; Kumar et al. 2014). Researchers routinely use indicative ratios of Phe/Ant to evaluate PAHs’ distribution and presumable sources in the environment (Magi et al. 2002). According to the Center for Children’s Environmental Health studies, children who are more prone to PAH exposure during pregnancy are liable for unfavorable birth outcomes such as birth underweight, early-maturing delivery, and organ defects. Prenatal PAH exposure is associated with a lowering IQ, behavioral difficulties, and childhood asthma in young children (Rengarajan et al. 2015; Perera et al. 2014). PAHs have been found at high concentrations in the marine ecosystem, including fish and benthic invertebrates (Chizhova et al. 2013; Honda et al. 2018; Hu et al. 2009; Kannan and Perrotta 2008; Miki et al. 2014; Pereira et al. 2009; Uno et al. 2010). PAHs in the aquatic environment are classified into four types: those that originated from fuels (petrogenic), combustion process (pyrogenic), organic metabolism (biogenic), and sediment conversion process (diagenetic) (Hylland 2006). Oil spill incidents are among the most disquieting vulnerability events for PAH contamination in aquatic environments (Hayakawa 2018; Koyama et al. 2004, 2016; Ladwani et al. 2013; Tronczyński et al. 2004; Uno et al. 2017). The carcinogenicity and mutagenicity of PAHs are the most concerning perspectives of their toxicity (Collins et al. 1998; Devi et al. 2016; Kuo et al. 1998; Rengarajan et al. 2015). Because of their hydrophobicity, PAHs are transported into cells and activate gene expression of the cytochrome P450 (CYP) (Bekki et al. 2013; Ikenaka et al. 2013; Jacob 2008; Jorgensen et al. 2008). PAHs are metabolized by CYP enzymes when they are expressed. It should be noted that various intermediates in this metabolic pathway have the potential to bind with DNA and become mutagenic/carcinogenic. Additional toxicological research has intimated that PAHs may cause developmental toxicity, genotoxicity, immunotoxicity, oxidative stress, and endocrine disruption (Bekki et al. 2009; Cherr et al. 2017; Hannam et al. 2010; Lee et al. 2011; MacDonald et al. 2013). PAHs have been studied for their carcinogenicity to animals, including humans. It has been shown that mutations generated by benzo[a]pyrene are a polycyclic aromatic hydrocarbon (PAH), and were responsible for 60% of lung cancer cases (Denissenko et al. 1996). BaP exposure dramatically enhances the mRNA levels of apoptotic genes such as p53, bax, and bcl-2 and the activity of caspases 3, 8, and 9 (Zha et al. 2017). Furthermore, there is a link between BaP-induced endoplasmic reticulum dysfunction and lipid metabolism (Cai et al. 2019). Embryotoxicity in experimental animals has been documented as a result of PAH exposure. PAHs may influence critical reproductive hormones such as LH, FSH, GnRH, and aromatase enzyme (Bolden et al. 2017). Moreover, it is well recognized that BaP provokes various carcinogenic effects in multiple cancer, including cervix, breast, and prostate cancer (Rengarajan et al. 2015; Abdel-Shafy and Mansour 2016; Verma et al. 2012). Besides, animal knock-out experiments showing that PAH exposure may disrupt the AhR-regulated gene expression needed for a cardiovascular system induce structural and functional alterations in bone marrow, deregulation of genes involved in ocular development, overexpressed cytochrome P450, which has serious health repercussions (Hrudkova et al. 2004; Holme et al. 2019; Magnuson et al. 2018; Burchiel and Luster 2001; Marris et al. 2020). In experimental animals, PAH exposure profoundly impacted hypertension linked to eNOS inactivation, resulting in the abolition of NO-mediated vaso-relaxation and increased blood pressure (Chang et al. 2017; Gentner and Weber 2011). Monohydroxylated PAHs (OHPAHs) proved to be hazardous in animals and may have a severe deleterious impact on vertebrate endocrine systems (Idowu et al. 2019; Hayakawa et al. 2006). In rat bone marrow cells, BaP was demonstrated to inhibit osteogenesis (Andreou et al. 2004). PAHs are hazardous to the gonads as well as the liver. BaP exposure affects the gene expression and androgen metabolic pathways in humans (Colli-Dula et al. 2018). Furthermore, PAHs have been linked to DNA damage prevalent in atherosclerosis, human endothelium, and smooth vascular muscle cells because of their mutagenesis properties (Zhang et al. 1998; Pulliero et al. 2015; Penn 1990). In cells, PAHs may absorb UVA light and generate reactive intermediates, damaging the cell membrane, DNA breakage, and protein degradation (Yu 2002; Yan et al. 2004). Long-term exposure to PAHs may cause tumor growth in many organs, including the lung, skin, esophagus, and breast cancer (Rajpara et al. 2017; Yu 2002).

5ClC

5ClC is the most prevalent chlorinated nucleobase. Mutagenesis of 5ClC is observed in inflammation-associated malignancies, and it crystallized human polymerase (pol) facing the lesion. 5ClC interacts with DNA methyltransferases, causes alterations in DNA methylation patterns, and blocks replication (Winterbourn and Kettle 2000; Kawai et al. 2004; Whiteman et al. 1997; Kang Jr and Sowers 2008; Mangerich et al. 2012; Knutson et al. 2013; Fedeles et al. 2015; Lao et al. 2009; Delaney and Essigmann 2006; Shrivastav et al. 2014; Li et al. 2014). According to both in vivo and in vitro data, 5ClC promotes base anti-conformation by preferring the major over minor DNA groove location. The constrained minor groove of most DNA polymerases, the anti-conformation of the 5ClC base, assumed to hold the 5Cl substituent in the DNA major groove, is a crucial constituent that develops a positive hydrogen-bonding interaction between 5ClC and the incoming dATP, which feasible forms the molecular evidence for 5ClC’s mutagenic mispairing ability and this kind of interaction and the configuration of a manifest a basic site templating pocket are enough to serve the mutagenic inclusion of dATP contrary 5ClC via an “enhanced A-rule” mechanism in which a polymerase includes an A converse structure that resembles a basic site (Li et al. 2014). The structural snapshots demonstrate that 5ClC assumes a conformation in which the 5Cl substituent is positioned in the groove of DNA during the mutagenic detour of the lesion (Fedeles et al. 2015). 5ClC joins many other substituted cytosine analogs identified as mutagenic and generates CT mutations. 5ClC may contribute C: GT: A transition mutations which identified in tissues exposed to chronic inflammation, increasing the likelihood those tissues may develop cancer (Sato et al. 2006; Sheh et al. 2010; Fedeles et al. 2015; Mangerich et al. 2012; Knutson et al. 2013; Sato et al. 2006; Sheh et al. 2010; Li et al. 2014).

Biodiesel

Fatty acid trans-esterification produces fatty acid methyl esters, which are used to make biodiesel. The effects of diesel exhaust from petroleum diesel engines on human health have received substantial attention since the first comprehensive toxicological research in 1986 (McClellan 1986). Particulate matter (PM) of diesel exhaust contributes to air pollution to varying degrees, especially in urban areas. Prolonged exposure to environmental PM, generated mainly by gasoline or diesel engines, is genotoxic to people (DeMarini 2013) and is found to be associated with an enhanced risk of asthma, lung cancer, and several cardiovascular diseases (Gichner 1991; Loprieno 1975). Several studies found that extractable organic compounds from biodiesel PM are much less oncogenic in the Salmonella (Ames) mutagenicity assay than those found in petroleum diesel pollutants (Mutlu et al. 2015). Recent research studies on rapeseed biodiesel showed just a minute change in mutagenicity in Salmonella and lethality in human embryonic renal 293T cells between peels and extracts of petroleum diesel as well as rapeseed biodiesel (Agarwal et al. 2018). One study revealed a substantial relationship between both the mutagenicity emission rate (rev/L) and the proportion of unsaturated fats using data from biodiesels made from linseed oil, rapeseed oil, coconut oil, and palm tree oil. As a function, the higher the proportion of double bonding in fatty acids, the higher the rate of mutagenicity generation (Bunger et al. 2016). When comparing biodiesels to petroleum diesel, the mutagenicity emission factors computed for canola, soy, and WVO under combustion conditions are often lower for biodiesels (DeMarini et al. 2019). According to a recent study, WVO may have the most negligible environmental impact and the most significant economic benefit compared to pure plant-derived fuels (Liang et al. 2013; Fawaz and Salam 2018). More study may aid in providing an additional full life-cycle review of biodiesel fuels and their mutagenicity and more evidence to help policy decisions on the encouragement and use of biodiesel fuels.

Multiple approaches to estimate mutagenic factors in the environment

Biological tests for mutagen detection are crucial in assessing materials generated from natural habitats. The test must be sensitive enough to identify typically meager amounts of mutagenic compounds prevalent in varied environments (Węgrzyn and Czyz 2003). The following approaches were used to estimate mutagenic factors in the environment as shown in Fig. 4.

Fig. 4
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Shows multiple detection test to estimate mutagenic factors in environment

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Ames test

The Ames test has earlier been used to evaluate the mutagenicity of thousands of compounds as shown in Fig. 5. This is an undeniable benefit since no other mutagenicity test now available can offer a comparable quantity of the sample for comparison reasons. In the research lab, the Ames test is suitable for determining the mutagenic activity of specific substances. However, there are just some challenges with using it in studies on various environmental samples. In this assay, genetically engineered S. typhimurium strains are employed. The existence of mutations in his genes, which induce anomalies in a metabolic pathway leading to the synthesis of histidine, enables positive selection of his+ revertants on minimal agar plates lacking histidine. Only mutants with his function restored can form colonies on such plates. Ordinarily, the tested medication and tester bacterium are cultivated for 48 h before measuring the bacterial colonies on the petri dishes. Although the sensitivity of the Ames test is suitable for assessing the mutagenicity of known compounds in the research lab, it could be too limited for identifying low amounts of mutagens in the samples of the environment (Węgrzyn and Czyz 2003; Ames et al. 1975).

Fig. 5
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Shows mechanism of Ames test to estimate mutagenic factors in environment

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Mutatox test

The Mutatox test is a commonly available microbial mutagenicity testing that uses a unique dark strain of luminous bacterial species (designated M169). The M169 strain is a darkish mutant with a genetic defect in the regulatory framework instead of one of the lux component genes’ coding sequences. In the existence of relatively low dosages of genotoxic substances in a growth media, light generation is regained in this variant. Mutatox can detect mutagens’ presence, comprising DNA-damaging agents, base substitution agents, DNA synthesis blockers, and DNA intercalating agents. The Mutatox test necessitates the use of certain materials and equipment, including Microtox Model 500 Analyzer, Mutatox reagent (freeze-dried M169 cells), dry test medium with and without rat-liver microsomal enzymes (S-9 mix), and suitable co-factors. In a hydrated Mutatox medium, dilutions of the analyzed substance are applied to the tester bacterial cells. Following a 24-h incubation period, light measurements are taken using the Microtox Model 500 Analyzer. Mutatox has been demonstrated to exhibit sensitivity comparable to the Ames test for both pure compounds and ambient specimens. Mutatox benefits from being simple to execute; nevertheless, specific equipment is required (it might be a logistical problem if unusual analyses are performed than normal genotoxic research). Although the whole assay may be completed in 24 h, which is an improvement over the Ames test (which requires plates to be incubated for 48 h), this is still not the fastest method (Schrader and Cooke 2003).

Molecular mechanisms of heavy metals induced DNA damage and its role in multiple disorders

Many environmental toxicants are genotoxic that cause DNA damage within the cell. Physical mutagens, chemical mutagens, heavy metals are usually implicated in DNA damage. Molecular mechanisms of heavy metals present in the environment are implicated in DNA damage and multiple disorders as shown in Fig. 6.

Fig. 6
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Shows mechanism the molecular mechanisms of heavy metals present in environment induced DNA damage and its role in multiple disorders

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Chromium

Chromium compounds are the most common inorganic environmental contaminants that interact with DNA, producing substantial DNA damage and leading to hazardous illnesses. Some of the ions are discharged into the environment by a variety of natural as well as anthropogenic sources such as rock component weathering and wet precipitation, and dry fallout from the sky is the primary source of Cr in natural and terrestrial systems (Kotas and Stasicka 2000). The organism can absorb chromium ions in three forms: via inhalation, oral administration, or percutaneous administration; however, the absorption efficacy is primarily determined by the oxidation grade of these compounds. Cr primarily occurs in two stable oxidation forms: Hexavalent (Cr (VI)) and trivalent (Cr (III)). Cr species are considered hazardous to various degrees at various phases; the reduction of Cr (VI) to Cr (III) generates free radicals inside. Trivalent Cr (Cr (III)) occurs as cationic species and is utilized as micronutrients and nutritional supplements required for insulin control and glucose metabolism. Cr (III) may induce hazardous consequences if present in high quantities owing to its capacity to coordinate diverse chemical molecules, resulting in inhibition of specific metalloenzyme systems (Shanker et al. 2005). Hexavalent (Cr (VI)), which is mostly anthropogenic in origin and exists as anionic species, is poisonous and proven as a human carcinogen (Sawicka et al. 2020; Hamilton et al. 2018). Chromium (VI) much more effectively enters the body via all three modes of exposure: inhalation, ingestion, and skin absorption compared to its trivalent state, and this might be related to its genotoxic impact. Chromium Cr (VI) may enter the cell via the sulfate-anion channel and be reductively metabolized to stable trivalent species Cr (III). Animals that are exposed to chromium (VI) in their drinkable water exhibited gastrointestinal malignancy, with linear and supralinear responses in the small intestine of mouse. At neutral pH, chromate, the most prevalent form of chromium (VI), is carried in by certain cells via sulfate routes and triggered non-enzymatically by small thiols and ascorbate. Cr (VI) metabolism in cells may result in both oxidative and non-oxidative DNA damage. Adducts of chromium-DNA are responsible for mutations and chromosomal shattering, and are the most common DNA damage caused by Cr (VI). Emerging data suggest that the two-way connections between epigenetic alterations and damage of DNA dictate the spectrum of genomic rearrangements and gene expression patterns in malignancies (Zhitkovich 2011). Chromate has been shown to create various DNA lesions, including DNA, DNA-protein, DNA-amino acid cross-links, single strand, and double breaks, as well as alkali labile places, which might influence to its mutagenic consequences (Błasiak and Kowalik 2000). Cr (VI) may cause various localized toxicities, including carcinogenicity, under certain extremely high-exposure situations. Some of this toxicity seems to be connected to its fast decrease, connected with oxidation of tissue components and subsequent tissue damage (O’ Flaherty et al. 2001). Recent research found that chromate exposure causes the production of Cr (III)–DNA adducts and Cr (III)-mediated cross-links of amino acids and glutathione with DNA. By changing the speed and fidelity of DNA replication, Cr (III) cross-links amino acids and glutathione with DNA, causing primary forms of DNA lesions that lead to mutagenesis and carcinogenesis (Khan et al. 2012). Scientists conducted a series of tests to investigate the interaction between DNA and the cancer-causing chromium Cr (VI). It has been discovered that a connection that is solely defined to the DNA nucleotide (guanine) sequence causes genetic modifications, because chromium converts the bases to 8-oxo-Guanine in order to have the oxidation of a specific site, the connection between the Cr (V) in complex form and the guanine base. The DNA damage site splits into two molecules. These two lesions were identified as guanidinohydantoin and spiroiminohydantoin after additional investigation. The DNA polymerase was paused, and adenine was added to the opposite location of the DNA to generate the 8-oxo-Guaniosine base. As a result, lesions are made up of G—>T transversions. Because of its high valent, chromium functions as a cancer-causing agent. Chromate exposure causes DNA damage, which leads to toxicity in humans. It demonstrates that Cr (V) interacts with xenobiotics that produce 8-oxo-Guaniosine (Morales et al. 2016; Sawicka et al. 2020). Hexavalent chromium (Cr (VI)) is recognized as an etiological factor for lung cancer, and Cr (VI) genotoxicity was also observed in bacterial and mammalian cell lines (Proctor et al. 2002). Numerous in vivo studies have found that Cr (III) and Cr (VI) both significantly induce genetic mutation in S. cerevisiae and induce damage of DNA inside both cells of Jurkat and yeast, suggesting that each may act as genotoxic substances. Additionally, Cr (III) has a greater influence than Cr (VI). According to the findings, Cr (III) simply disturbs with base-pair mounting, whereas Cr (VI) presumably intercalates further into spaces between base pairs of DNA (Fang et al. 2014). Cr (VI) may be converted to trivalent chromium, leading to ROS generation such as H2O2, OH•, and O2. ROS-regulated redox-sensitive protein kinases and transcription factors, such as those implicated in the Akt, NF-B, and MAPK pathways, may influence the release of cytokines such as TNF and IL-1 in specific kinds of cells (Wang et al. 2010).

Arsenic

Arsenic seems to be the twentieth very common constituent of the mother earth’s mantle. Much of this is obtained in the oxide and sulfide forms, although it is also seen as salts with sodium, copper, and iron, which is poisonous and causes multiple diseases. Arsenate and arsenate these two inorganic forms of arsenic that are hazardous to humans and the environment (Morales et al. 2016). Arsenic may enter the body via a variety of natural and industrial sources via uncommon routes. Pesticides containing arsenical compounds and unintentional discharge of such chemicals and certain mineral deposits may pollute drinking water. Arsenic is a protoplasmic toxin that affects the sulfhydryl group of cells, causing cell respiration and mitosis to fail. It also has an impact on enzymes, and poisoning of arsenic may cause skin problems, cancer, cognitive problems, cardiovascular problems, and diabetes which makes it an incurable illness (Morales et al. 2016).

Lead

Human exposure to lead compounds is owing to their usage in paints, cosmetics, toys, home dusting material, polluted soil, and industrial emissions. Drinking water may potentially be poisonous due to lead contamination and exposure of lead affecting humans’ neurological systems and gastrointestinal tract. According to the Environmental Protection Agency, lead is a carcinogenic chemical. Lead poisoning is another term for lead toxicity, which may cause chronic or acute ailments such as lack of appetite, stomach discomfort, sleeplessness, arthritis, renal abnormalities, and exhaustion (Jan et al. 2015).

Mercury

Mercury is the most dangerous heavy metal present in the environment as a result of numerous activities. The level of mercury is very high, especially in marine foods, and its exposure is widely established to cause acute heavy metal toxicity. Mercury (Hg), both organic and inorganic, combined with other elements leads to brain damage, kidney damage, and renal failure. It may also induce a disruption in calcium homeostasis, protein denaturation by interfering with its activity, and disrupts transcription and translation by causing ribosomes and endoplasmic reticulum to disintegrate. Microtubule destruction and mitochondrial damage inside cells and oxidative oxidation of fluids is caused by neurotoxin compounds such as methyl mercury (Compeau and Bartha 1985).

Cadmium

Cadmium (Cd) is a toxic heavy metal concern for many researchers, and it has been studied in a wide range of species, including algae, crustaceans (shrimps), rodents (mice), amphibians (tadpoles), and mammals (Lu et al. 2021; Verheyen and Versieren 2014; Zhang et al. 2021; Liu et al. 2014). Cadmium is released into the environment through both anthropogenic (farming, activities in urban areas, and toxic waste discharges from industry, charcoal ashes lagoons, combustion of fossil fuels, burning, and municipal hazardous effluent) and natural (erosion and weathering of soil and rock conditions, natural burning from volcanic eruptions and forest fires) processes (Mouchet et al. 2006). It may enter cells in various methods, including ion membrane transfer and passive diffusion of neutral chemical species. In cells, they may enhance the generation of reactive oxygen species (ROS) and therefore cause oxidative stress, leading to lipid peroxidation in mitochondria and, ultimately, one of the final phases of cell damage is the generation of the cytochrome C. Xenopuslaevis exposing to ecologically Cd produce genotoxicity through oxidative stress, DNA binding, or inhibition of DNA repair processes (Mouchet et al. 2006). Recent investigations on Cd toxicity on gut flora demonstrated that Cd stress significantly decreased the development rate of gut microbiota in vitro (Liu et al. 2014). Cd has been identified as a human carcinogen and may induce a broad range of toxicological effects on aquatic creatures, including alterations in physiological and biochemical processes, energy metabolic dysfunction, histopathological damage, DNA damage, and growth suppression. Chronic exposure to non-lethal cadmium doses (3 M and 5 M) resulted in petite mutants in addition to nuclear alterations (Zhang et al. 2021; Liu et al. 2014; Jin et al. 2003). A growing number of studies have shown early detrimental health consequences from cadmium exposure at far lower levels than previously thought. The majority of the research has focused on kidney and bone impacts, but new studies have also shown increased cancer risks with low-level environmental exposure. Cadmium has a lengthy biological half-life in the human kidneys, lasting 10–30 years. Chronic low levels of Cd can cause renal failure, unregulated blood pressure, diabetes problems, and bone structural changes, resulting in osteoporosis. Furthermore, Cd has been linked to airway inflammation, cardiovascular disease, diabetes, neurological disorders, and several malignancies (Liu et al. 2014; Messner and Bernhard 2010; Jarup and Akesson 2009; Johri et al. 2010). Chronic Cd exposure and toxicity have the most significant impact on the kidney. Cd accumulates in the kidney due to receptor-mediated endocytosis of freely filtered and metallothionein-bound Cd (Cd-MT) in the proximal renal tubule (Jarup and Akesson 2009; Johri et al. 2010). Since the 1950s, it has been known that extended exposure to high cadmium levels may cause bone disease, which has initially been recorded from the Jinzu river basin in Japan. Multiple fractures and deformation of the long bones in the skeleton define itai-itai (“ouch-ouch”) illness, which causes intense discomfort in afflicted persons. The International Agency for Research on Cancer (IARC) classified cadmium as a human carcinogen (class I) in the year 1993, based on substantial evidence indicating carcinogenicity in both people and experimental animals. According to recent research, cadmium may have a role in coronary heart disease (Jarup and Akesson 2009; Everett and Frithsen 2008). Cadmium inhibits the ability of minor misalignments and base-base mismatches to be repaired post-replication mismatch repair (MMR). Cadmium hindered at least one process leading to mismatch elimination in human cell extracts. Several findings reveal that an environmental hindrance to a mutation-avoidance mechanism might result in a high amount of genomic instability (Jin et al. 2003).

Aluminum

Aluminum is the third most prevalent element in the earth’s crust. Aluminum ingestion admission into the human body occurs mainly by skin contact, inhalation, and other means. Symptoms of high aluminum content in the body include vomiting, ulcers, skin rashes, and bone discomfort. These symptoms last just a short time. Aluminum poisoning is caused by a dusty atmosphere, renal disease, and polluted water. The aluminum buildup causes interactions between aluminum and the plasma membrane and apoplastic and symplastic targets. In humans, Al+3 replaces Mg+3, producing problems with intermolecular and intercellular communication, cell development, and secretary functions (Jan et al. 2015).

Environmental mutagens and their role in multiple disorders in humans

Various environmental mutagens such as radiation, chemical, and biological agents are responsible for multiple human disorders as shown in Table 2. Radiation is induced by X-rays, and UV rays prompt bone cancer, breast tumors, enlarged hearts, blocked blood vessels, and several infectious diseases (Morley 2012). 8-oxoG promotes cancer and neurodegeneration by accumulating in mitochondrial DNA of neurons, resulting in calpain-dependent neuronal death. Delayed nuclear deposit of 8-oxoG in microglia results in PARP-dependent production of an apoptosis-inducing signal and worsening of microgliosis (Sheng et al. 2012). Cadmium accumulates mainly in the liver and kidneys, binds to metallothionein in the blood, moves to the glomerulus, and is secreted from the tubular cells of the kidneys. Cadmium accumulates in the renal cortex and inhibits metal-dependent enzymes or activates calmodulin, which regulates smooth muscle contraction by sensing calcium levels. When the kidneys are significantly injured, they begin to suffer from a musculoskeletal injury due to calcium homeostasis disruption. The bone pain and abnormalities that define Itai-Itai illness are caused by musculoskeletal injury (Nishijo et al. 2017). Contact dermatitis, bronchial asthma, allergic rhinitis, and contact allergic eczemas are caused by chromium exposure. While causing contact dermatitis, it predominantly affects keratinocytes. These cells can be directly activated by expressing the membrane antigen ICAM-I, a ligand for the leucocyte antigen LFA-I, and releasing cytokines, including a substantial release of TNF-alpha (Shrivastav et al. 2014). BPA generated multiple diseases such as angina, coronary arterial disease, hypertension, heart attack, and atherosclerosis. Many signaling pathways are activated by low-dose BPA exposure, including Protein Kinase A (PKA) and Ca2+/CaM-dependent protein kinase II (CAMKII). Acute BPA exposure increased cAMP production, PKA activation, and phosphorylation of the ryanodine receptor (RyR). BPA also stimulates phospholipase C (PLC), which leads to the formation of triphosphoinositol (IP3), IP3 receptor-mediated Ca2+ release, most likely from endoplasmic reticulum Ca2+ storage, and activates CAMKII, which phosphorylates phospholamban (PLN). Phosphorylation of RyR enhanced channel opening and SR Ca2+ leak, whereas phosphorylation of PLN resulted in PLN inhibition of Sarco/Endoplasmic Reticulum Ca2+-ATPase (SERCA) and enhanced SR Ca2+ reuptake (Gao and Wang 2014). Mercury is the cause of pneumonitis, non-cardiogenic pneumonitis, pulmonary edema, and acute respiratory distress. It disrupts normal cell physiology in various organ systems, often by covalently binding to sulfhydryl-containing enzymes and proteins within the cell. Inhaling high-temperature vapor damages lung tissue thermally, whereas oxidized mercury ions cause direct airway irritation and cellular poisoning. Mercury travels through the alveolar membrane during breathing, resulting in rapid systemic absorption and extensive dispersion throughout organs (Glezos et al. 2006). Lead is responsible for hypertension, coronary heart disease, stroke mortality, and peripheral arterial disease. The reduction in renal function caused by lead may play a substantial influence in hypertension. It also causes an increase in oxidative stress. It also increases the activity of the renin-angiotensin system. Nitric oxide and soluble guanylate cyclase are both inhibited. It influences heart rate variability by interfering with autonomic nerve control of the heart (Navas-Acien et al. 2007). Arsenic can cause blackfoot disease, skin cancer, and lung cancer. The effects of arsenic on hypercoagulability, endothelial damage, smooth muscle cell proliferation, somatic mutation, oxidative stress, and apoptosis may be connected to arsenic atherogenicity. Its interactions with various trace elements and its links to hypertension and diabetes may explain a portion of its elevated risk of atherosclerosis. It disrupts DNA repair mechanisms, increasing chromosomal abnormalities (Tseng 2005; Pershagen 1981). Aluminum is responsible for acute encephalopathy and Alzheimer’s disease. Aluminum accumulation in the brain’s gray matter has been related to acute aluminum neurotoxicity. Aluminum acute poisoning can result in confusion, delirium, tremors, hallucinations, and slurred speech and trigger neurotoxicity in humans. In order to actively transverse brain borders, Al sequesters multiple transport mechanisms. Small amounts of Al absorbed progressively during a lifetime promote preferential accumulation in brain tissues (Malaki 2013; Tomljenovic 2011).

Table 2 Shows the role of environmental mutagens in multiple disorders in humans
Full size table

Future perspectives

Environmental mutagens comprise chemical and physical substances in the environment that can alter genetic material and cause mutations and a variety of negative consequences on human and animal health. Most mutagens are carcinogenic in humans or even have genotoxic effects on the following generation via germ cells. These mutagens have been associated with multiple neurological disorders. Various unresolved environmental challenges with mutagens exist all around the world and become study topics. To expedite environmental mutagen investigation, scientists in this field should make an effort to utilize modern tactics, prominently scientific instruments and molecular and cellular biology techniques, and must use artificial intelligence and information technology, which will open up new research areas in the field. Researchers from multiple disciplines must consider exchanging mutually beneficial ideas that are more prominent than competitiveness to research at a higher level. Furthermore, there is a need to understand the molecular basis of epigenetic regulation and how it is critical to incorporate biological control into the repertoire of environmental health research and medicine, thus, focusing on the cutting-edge study of the genetic and epigenetic consequences of environmental mutagens and carcinogens.

Conclusion

Exposure of humans and animals to environmental mutagens has indeed been documented, but more study is needed. A few of them, such as chromium, are necessary for humans, although they are also hazardous due to a variety of action mechanisms. Most mutagens are carcinogenic in humans or have genotoxic effects on the following generation through germ cells. For the detection of environmental mutagens, several different kinds of biological systems have been utilized. Each system has its own set of pros and downsides. Heavy metals may cause genetic damage by causing double-strand breaks (DSBs) and blocking key proteins from various DNA repair pathways. Arsenic is mutagenic to endogenous genes in mammalian cells, causing typically massive multilocus deletions mediated by ROS. The ionic process of oxidative stress is followed by lead metal. Human cells are harmed as a result of this process. Mercury is the most dangerous heavy metal present in the environment. Mercury compounds are very carcinogenic, and the human brain system is very susceptible to any and all mercury compounds. Mercury buildup may disrupt brain functioning, causing memory issues as well as alterations in vision or hearing. Cadmium causes apoptosis in cells. Cadmium poisoning results from DNA strand breaks. Cadmium carcinogenesis is caused by a number of mechanisms, including DNA repair inhibition. Exposure to cadmium may cause genomic mutations and hyper mutability of mismatch repair depression in yeast. Cr III interferes with the interaction of the DNA template and the polymerase, which leads to chromium-mediated carcinogenesis. Al has been shown to have pro-oxidant action, enhancing cellular oxidation by superoxide and iron. Al induces the expression of oxidative distress in plants and stimulates antioxidant defense network. Mycotoxin is a diverse group of naturally occurring fungus secondary metabolites having harmful effects on humans and animals. Aflatoxins, ochratoxin A, sterigmatocystin, and numerous other mycotoxins have been identified as carcinogenic; numerous others have been proven to be mutagenic. Electromagnetic, ionizing radiations, such as X-rays and rays released by radioisotopes, and UV light are the most often employed types of physical mutagens, as are particle radiations such as fast and thermal neutrons and beta and alpha particles. Assimilation of sunlight effectively destroys DNA, and the large proportions of these illnesses are clearly caused by wavelengths of UVB and UVA. Tobacco, DMS, BPA, 8-Oxog, PAHs, and 5-CIC are all exceedingly genotoxic. Tobacco smoke is the most potent human mutagen in the system. BPA affects cell transformation as well as other genetic consequences. Reactive oxygen species produced inside the mammalian cell may result in 8-oxoG in mRNA, causing base mispairing during gene translation. The buildup of 8-oxoG in mRNA may affect protein synthesis in mammalian cells. PAHs are widespread environmental pollutants that are being fabricated mostly as a result of deficient combustion of organic compounds as well as have poisonous, mutagenic, and/or carcinogenic effects. 5-Chlorocytosine is innately miscoding during DNA replication, and it may cause a high frequency of C-to-T mutations, a form of mutation that is common in human malignancies. Preliminary biological tests are performed to determine the presence of mutagenic chemicals. Following that, if required, a full chemical analysis may be undertaken to establish the precise kind of mutagen.