Summary
Dilute aqueous solutions of biologically active DNA can serve as a simplified model system of the cell. As a biological endpoint the survival of the DNA (after transfection to E. coli spheroplasts) is used. Damage in the DNA, irradiated in water with gamma rays, can be ascribed to reactions with primary waterradicals. By introducing additives in such solutions, which will scavenge the primary waterradicals, competition between a scavenger and DNA for such radicals can be studied. Comparison of different additives makes it possible to decide whether a compound behaves like a simple scavenger, radiosensitizer or like a radioprotector. In this context work has been done with the electron-affinic radiosensitizers metronidazole, misonidazole and nifuroxime. We have found that these wellknown cellular sensitizers do not enhance the inactivation of biologically active DNA. They act as simple competitive scavenger for waterradicals. However, if besides a sensitizer a trace of a metalloporphyrin containing compound (e.g. cyt. c) is present during irradiation an enhanced DNA inactivation, which can be interpreted as sensitization, is observed. Without sensitizer metalloporphyrins induce an enhanced protection of DNA.
Apart from these effects the consequences of both chemical-(sulphy-dryl) and enzymatic-(excision; recombination) repair has been studied. It has been found that sulphydryl compounds are able to react with DNA radicals, modifying the radiation damage in such a way that e.g. breaks are prevented. Further in double-stranded DNA a considerable amount of OH and also H radical damage appeared to be reparable by the excision-repair mechanism. However, post-replication repair had only very small or no effect on the amount of damage.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Adams GE, Mc Naughton GE, Michaels BD (1968) Pulse radiolysis of Sulphur Compounds II. Free radical “Repair” by hydrogen transfer from sulphydryl compounds. Trans Faraday Soc 60:902–911
Blok J (1967) Lethal and mutagenic action of γ-rays on bacteriophage DNA. In: Silini G (ed) Proceedings of the Third International Conference on Radiation Research, pp 423–437
Blok J, Loman H (1973) The effect of γ-Radiation in DNA. Curr Top Radiat Res Q 9:165–245
Dizdaroglu M, Schulte-Frohlinde D, Sonntag C von (1977a) Isolation of 2-dexoy-D-erythio-pentoic acid from an alkali-labile site in γ-irradiated DNA. Int J Radiat Biol 32:481–483
Dizdaroglu M, Schulte-Frohlinde D, Sonntag C von (1977b) γ-radiolysis of DNA in Oxygenated Aqueous Solution. Structure of an alkali-labile site. Z Naturforsch 32:1021–1022
Fielden EM, Sapora O, Loverock PM (1978) The effect of the electron affinic sensitizers Ro 07-0582 and Ro 03-6156 on the survival of several E. coli mutants. Int J Radiat Biol 33:41–45
Hemmen J van, Meuling WJA, Schans GP van der, Bleichrodt JF (1974a) On the mechanisms of sensitization of living cells towards ionizing radiation by oxygen and other sensitizers. Int J Radiat Biol 25:399–402
Hemmen J van, Meuling WJA, Bleichrodt JF (1974b) Radiosensitization of biologically active DNA in cellular extracts by oxygen. Evidence that the presene of SH-compounds is not required. Int J Radiat Biol 26:547–555
Hemmen J van, Meuling WJA, Bleichrodt JF (1978) Effect of oxygen on inactivation of biologically active DNA by γ-rays in vitro: Influence of Metalloporphyrins and enzymatic DNA repair. Radiat Res 75:410–423
Howard-Flanders P (1960) Effect of oxygen on the radiosensitivity of phage in the presence of SH compounds. Nature 186:485–487
Hutchinson F (1961) Sulphydryl groups and the oxygen effect on irradiated dilute solutions of enzymes and nucleic Acids. Radiat Res 14:721–731
Jong J de, Loman H, Blok J (1972) Host-cell reactivation of φX174 RF-DNA damaged by γ-ray-induced phenylalanine and water-radicals. Int J Radiat Biol 22:579–587
Lafleur MVM, Loman H, Blok J (1975) On the role of phosphate in the irradiation of DNA in aqueous solution. Int J Radiat Biol 27:197–200
Lafleur MVM, Woldhuis J, Loman H (1980) Effects of sulphydryl compounds on the radiation damage in biologically active DNA. Int J Radiat Biol 37:493–498
Lafleur MVM, Loman H (1982) Infuence of anoxic sensitizers on the radiation damage in biologically active DNA in aqueous solution. Int J Radiat Biol 41:295–302
Lafleur MVM, Pluijmackers-Westmijze EJ, Loman H (1982a) Effects of oxygen and misonidazole on radiation damage in biologically active DNA dissolved in a bacterial extract. Influence of cytochrome c. Int J Radiat Biol 42:297–303
Lafleur MVM, Pluijmackers-Westmijze EJ, Loman H (1982b) Radiosensitization of single-stranded φX174 DNA in aqueous solution by misonidazole is induced by metalloporphyrins. Int J Radiat Biol 42:577–579
Lafleur MVM, Pluijmackers-Westmijze EJ, Loman AC, Loman H (1983) The role of metalloporphyrins in sensitization and protection fo single-stranded DNA. In: Broerse JJ, Barendsen GW, Kal HB, Kogel AJ van der (eds) Proceeding of the seventh International Congress of Radiation Research. Martinus Nijhoff publishers, The Hague Boston London, pp A 3–24
Lafleur MVM, Pluijmackers-Westmijze EJ, Loman H (1984) Contrasting effects of cytochrome c on the radiosensitivity of single-stranded φX174 DNA in the presene of misonidazole or phenol under Anoxia. International Journal of Radiation Oncology. Biol Phys 10:1195–1197
Lafleur MVM, Pluijmackers-Westmijze EJ, Loman AC, Loman H (1985) Adduct formation is involved in radiosensitization, mediated by cytochrome c, of φX174 DNA by misonidazole. Int J Radiat Biol 47:379–382
Michaels HB, Rasburn EJ, Hunt JW (1976) Interaction of the Radiosensitizer paranitroacetophenone with Radiation-induced Radicals on Nucleic Acid Components. Radiat Res 65:250–267
Moan J, Pettersen EL (1981) X-irradiation of human cells in culture in the presence of haematorporphyrin. Int J Radiat Biol 40:107–109
Moore BA, Palcic B, Skarsgard LD (1976) Radiosensitizing and toxic effects of the 2-Nitroimidazole Ro 07-0582 in hypoxic mammalian cells. Radiat Res 67:459–473
Nabben FJ, Karman JP, Loman H (1982) Inactivation of biologically active DNA by hydrated electrons. Int J Radiat Biol 42:23–30
Nabben FJ, Lafleur MVM, Sikkers JCM, Loman AC, Retèl J, Loman H (1984) Repair of damage in double-stranded φX174 (RF) DNA due to radiation-induced waterradicals. Int J Radiat Biol 45:379–388
Sonntag C von (1984) Carbohydrate radicals: from ethylene glycol to DNA strand breakage. Int J Radiat Biol 46:507–519
Tsutsui M, Carrano CJ, Tsutsui EA (1975) Tumour localizers: Porphyrins and realted compounds (unusual metalloporphyrins XXII) New York Academy of Science, 244:674
Van Rijn K, Mayer R, Blok J, Verberne JB, Loman H (1985) Reaction rate of OH radicals with φX174 DNA: Influence of salt and scavenger. Int J Radiat Biol 47:309–317
Verberne JB (1981) A pulse radiolysis study of the electron reaction in aqueous solution and ice. Some experimental and theoretical aspects. Thesis,Vrije Universiteit, Amsterdam, The Netherlands
Verberne JB, Lafleur MVM, Hummel A, Loman H (1986) Radiation chemistry and biological effects. Non-homogeneous kinetics of reactions of waterradicals with biologically active DNA. Int At Energy Agency Panel Proc Ser (in press)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lafleur, M.V.M., Loman, H. Radiation damage to φX174 DNA and biological effects. Radiat Environ Biophys 25, 159–173 (1986). https://doi.org/10.1007/BF01221222
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01221222