Abstract
Ionizing radiation induces DNA damage, which generates a complex array of genotoxic responses. These responses depend on the type of DNA damage, which in turn can lead to unique cellular responses. High LET radiation results in clustered damages. This evokes specific signaling responses, which can be cytotoxic or cytoprotective in nature. In the present study the effect of carbon ion irradiation on p44/42 MAPK and NF-κB, which are essentially survival factors, have been studied. Moreover, the effect of inhibition of DNA-PK, which is an important component of DNA repair mechanism, with wortmanin on these signaling factors has been studied. The expression of p44/42 MAPK was different at 0.1 Gy and 1 Gy and wortmanin was found to inhibit its expression. NF-κB expression was higher at 1 Gy than at 0.1 Gy and its expression is unaffected by inhibition of DNA-PK. The notable findings of this study are that the responses to high and low dose of high LET radiation are essentially different and the 6 h time point post irradiation is crucial in deciding the response and needs further investigation. (Mol Cell Biochem 276: 169–173, 2005)
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
United Nations Scientific Committee on the Effects of Atomic Radiation: Report to the general assembly, United Nations, New York, 1993
National Research Council: Committee on Biological Effects of Ionising Radiation, Health Effects of Exposure to Radon (BIER VI). National Academy Press, Washington, DC, 1999
Prise KM, Ahnstrom G, Belli M, Carlsson J, Frankenberg D, Kiefer J, Lobrich M, Michael BD, Nygren J, Simone G, Stenerlow B: A review of dsb induction data for varying quality radiations. Int J Radiat Biol 74: 173–184, 1998
Tilly N, Fernandez-Varea JM, Grusell E, Brahme A: Comparison of Monte Carlo calculated electron slowing-down spectra generated by 60 Co gamma-rays, electrons, protons and light ions. Phys Med Biol 47: 1303–1319, 2002
Goto S, Watanabe M, Yatagai F: Delayed cell cycle progression in human lymphoblastoid cells after exposure to high-LET radiation correlates with extremely localized DNA damage. Radiat Res 158: 678–686, 2002
Ritter S, Nasonova E, Furusawa Y, Ando K: Relationship between aberration yield and mitotic delay in human lymphocytes exposed to 200 MeV/u Fe-ions or X-rays. J Radiat Res (Tokyo) 43: S175–S179, 2002
Powell SN, Kachnic LA: Roles of BRCA1 and BRCA2 in homologous recombination, DNA replication fidelity and the cellular response to ionizing radiation. Oncogene 22: 5784–5791, 2003
Yacoub A, Park JS, Qiao L, Dent P, Hagan MP: MAPK dependence of DNA damage repair: ionizing radiation and the induction of expression of the DNA repair genes XRCC1 and ERCC1 in DU145 human prostate carcinoma cells in a MEK1/2 dependent fashion. Int J Radiat Biol 77: 1067–1078, 2001
Kirchgessner CU, Patil CK, Evans JW, Cuomo CA, Fried LM, Carter T, Oettinger MA, Brown JM: DNA-dependent kinase (p350) as a candidate gene for the murine SCID defect. Science 267: 1178–1183, 1995
Lucke-Huhle C: Similarities between human ataxia fibroblasts and murine SCID cells: high sensitivity to gamma rays and high frequency of methotrexate-induced DHFR gene amplification, but normal radiosensitivity to densely ionizing alpha particles. Radiat Environ Biophys 33: 201–210, 1994
Holgersson A, Jernberg AR, Persson LM, Edgren MR, Lewensohn R, Nilsson A, Brahme A, Meijer AE: Low and high LET radiation-induced apoptosis in M059J and M059K cells. Int J Radiat Biol. 79: 611–621, 2003
Dent P, Yacoub A, Fisher PB, Hagan MP, Grant S: MAPK pathways in radiation responses. Oncogene 22: 5885–5896, 2003
Abbott DW, Holt JT: Mitogen-activated protein kinase kinase 2 activation is essential for progression through the G2/M checkpoint arrest in cells exposed to ionizing radiation. J Biol Chem 27: 2732–2742, 1999
Goodhead DT: Mechanisms for the biological effectiveness of high-LET radiations. J Radiat Res 40(Suppl): 1–13, 1999
Narang H, Krishna M: Mitogen-Activated Protein Kinases: specificity of Response to Dose of Ionizing Radiation in Liver. J Radiat Res 45: 213–220, 2004
Suzuki K, Kodama S, Watanabe M: Extremely low-dose ionizing radiation causes activation of mitogen-activated protein kinase pathway and enhances proliferation of normal human diploid cells. Cancer Res 61: 5396–5401, 2001
Schmidt-Ullrich RK, Dent P, Grant S, Mikkelsen RB, Valerie K: Signal transduction and cellular radiation responses. Radiat Res 153: 245–257, 2000
Hagan M, Wang L, Hanley JR, Park JS, Dent P: Ionizing radiation-induced mitogen-activated protein (MAP) kinase activation in DU145 prostate carcinoma cells: MAP kinase inhibition enhances radiation-induced cell killing and G2/M-phase arrest. Radiat Res 153: 371–383, 2000
Deak M, Clifton AD, Lucocq LM, Alessi DR: Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB. EMBO J 17: 4426–4441, 1998
Prasad AV, Mohan N, Chandrasekar B, Meltz ML: Activation of nuclear factor kappa B in human lymphoblastoid cells by low-dose ionizing radiation. Radiat Res 138: 367–372, 1994
Raju U, Gumin GJ, Noel F, Tofilon PJ: IkappaBalpha degradation is not a requirement for the X-ray-induced activation of nuclear factor kappaB in normal rat astrocytes and human brain tumour cells. Int J Radiat Biol 74: 617–624, 1998
Basu S, Rosenzweig KR, Youmell M, Price BD: The DNA-dependent protein kinase participates in the activation of NF kappa B following DNA damage. Biochem Biophys Res Commun 247: 79–83, 1998
Blakely EA, Kornenberg A: Heavy-ion radiobiology: new approaches to delineate mechanisms underlying enhanced biological effectiveness. Radiat Res 150: S126–S145, 1998
Wang Y, Meng A, Lang H, Brown SA, Konopa JL, Kindy MS, Schmiedt RA, Thompson JS, Zhou D: Activation of nuclear factor kappaB in vivo selectively protects the murine small intestine against ionizing radiation-induced damage. Cancer Res 64: 6240–6246, 2004
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Mitra, A.K., Bhat, N., Sarma, A. et al. Alteration in the expression of signaling parameters following carbon ion irradiation. Mol Cell Biochem 276, 169–173 (2005). https://doi.org/10.1007/s11010-005-3903-5
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s11010-005-3903-5