Induction and repair of DNA damage in gamma-irradiated human lymphoblasts: irradiation in the presence and absence of misonidazole.
The effects of oxygen and misonidazole on the induction of DNA lesions were examined in human TK6 lymphoblasts irradiated with 60Co gamma rays. We have investigated both the formation and subsequent repair of two classes of DNA damage, single-strand breaks and lesions recognized by the gamma endonuclease activity in a cell-free extract of Micrococcus luteus. Relative to irradiation under hypoxia, single-strand break yields were increased by the presence of either oxygen or misonidazole at the time of irradiation. In contrast, M. luteus enzyme-sensitive site yields were unaffected by the presence of either oxygen or misonidazole. No significant differences in single-strand break or enzyme-sensitive site repair kinetics were observed for lesions induced under any of the irradiation conditions employed. These results confirm the sensitizing effects of oxygen and oxygen-mimetic drugs on the induction of single-strand breaks but provide no support for their ability to enhance the induction of enzyme-sensitive sites.
Hentosh
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Laboratory of Radiobiology, Harvard University School of Public Health, Boston, Massachusetts 02115.
D001402:B-Lymphocytes / Q000528:radiation effects*; D002460:Cell Line; D003037:Cobalt Radioisotopes; D004247:DNA / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D004706:Endodeoxyribonucleases / Q000378:metabolism; D005720:Gamma Rays; D006801:Humans; D008920:Misonidazole / Q000494:pharmacology*; D010100:Oxygen / Q000494:pharmacology
D003037:Cobalt Radioisotopes; D008920:Misonidazole; D004247:DNA; D004706:Endodeoxyribonucleases; C044931:gamma endonuclease, Micrococcus luteus; D010100:Oxygen