DIFFERENTIAL REPAIR OF RADIATION-INDUCED DNA-DAMAGE IN CELLS OF HUMANSQUAMOUS-CELL CARCINOMA AND THE EFFECT OF CAFFEINE AND CYSTEAMINE ON INDUCTION AND REPAIR OF DNA DOUBLE-STRAND BREAKS

The goal of these experiments was to investigate further the relations hip between DNA double-strand breaks and cell killing in human tumor c ells, first by comparing different cell lines, and second by radiomodi fication studies. Field-inversion gel electrophoresis was used to quan tify double-strand breaks. Two subclones of the radioresistant human s quamous cell carcinoma line SQ20B (SQD9 and SQG6) were compared. These subclones differed in DNA index by a factor of 1.7 but showed the sam e resistance to radiation as cells of the parental cell line. It was f ound that, although induction of DSBs was not significantly different in the two cell lines, the t(1/2) of the fast component of repair was significantly shorter for SQD9 cells, leading to greater overall repai r which was not reflected in increased survival. Caffeine and cysteami ne were tested as modifiers of radiosensitivity, using the radioresist ant SQ20B line and the radiosensitive SCC61 cell line. No effect of ca ffeine was seen when the drug was present only during irradiation. Pos tirradiation incubations with caffeine, however, resulted in a dose re duction factor greater than 2.0 in cell survival for both cell lines. In contrast, induction of DSBs was reduced by caffeine, and no effect on DSB repair was observed. Cysteamine led to a dose protection factor greater than 1.8 in cell survival in both cell lines. A reduction in induced DSBs was found at high doses corresponding approximately with the increase in cell survival. Over the same (low) dose range, however , the correlation between DSB induction and cell killing was poor. The se data indicate that DSB induction does not correlate well with cell killing either for different cell lines, for radiochemical modificatio n (cysteamine) or for some other types of modification (caffeine).