Susceptibility to fluorescent light-induced chromatid breaks associated with DNA repair deficiency and malignant transformation in culture.
The increased susceptibility of mouse cells to fluorescent light-induced chromatid damage following their spontaneous malignant transformation in culture could result from loss or inactivation of catalase that decomposes the photoproduct H2O2 or from impaired capacities to repair DNA damage. No consistent change in catalase activity with respect to neoplastic state could be established. To interpret the cytogenetic damage in terms of DNA strand breaks, we determined the incidence of chromatid breaks induced by light exposure during the G1 and late S-G2 phases of the cell cycle in normal and malignant derivatives of a C3H mouse cell line. Chromatid breaks at metaphase following light exposure during G1 would result from DNA strand breaks, cross-links, or base damage, whereas breaks following exposure during late S-G2 would result from single-or double-strand breaks. Both G1 and late S-G2 were susceptible in malignant cells but only G1 in normal. Since caffeine inhibits DNA repair, we compared its effects on light-induced chromatid damage in the normal and malignant cells to assess their DNA repair capacities. Treatment of normal cells with caffeine (50 microgram/ml) directly following five hr of light exposure in G1 increased the chromatid damage to that in malignant cells exposed with or without caffeine. Similarly, treatment of normal cells with caffeine during late S-G2 exposure increased chromatid damage to a level not significantly different from that in malignant cells exposed without caffeine. Caffeine had little influence on chromatid damage in malignant cells. The increased susceptibility of malignant mouse cells to fluorescent light-induced chromatid breaks thus appears to result from impaired capacities to repair DNA damage.
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D002453:Cell Cycle; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002842:Chromatids / Q000528:radiation effects*; D002869:Chromosome Aberrations; D004260:DNA Repair; D007399:Interphase; D008027:Light; D051379:Mice
D002110:Caffeine; D002374:Catalase