Differential repair of radiation-induced DNA damage in cells of human squamous 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 relationship between DNA double-strand breaks and cell killing in human tumor cells, first by comparing different cell lines, and second by radiomodification studies. Field-inversion gel electrophoresis was used to quantify double-strand breaks. Two subclones of the radioresistant human squamous cell carcinoma line SQ20B (SQD9 and SQG6) were compared. These subclones differed in DNA index by a factor of 1.7 but showed the same resistance to radiation as cells of the parental cell line. It was found that, although induction of DSBs was not significantly different in the two cell lines, the t1/2 of the fast component of repair was significantly shorter for SQD9 cells, leading to greater overall repair which was not reflected in increased survival. Caffeine and cysteamine were tested as modifiers of radiosensitivity, using the radioresistant SQ20B line and the radiosensitive SCC61 cell line. No effect of caffeine was seen when the drug was present only during irradiation. Postirradiation incubations with caffeine, however, resulted in a dose reduction 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. These data indicate that DSB induction does not correlate well with cell killing either for different cell lines, for radiochemical modification (cysteamine) or for some other types of modification (caffeine).
Smeets
M F
MF
Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam.
Mooren
E H
EH
Abdel-Wahab
A H
AH
Bartelink
H
H
Begg
A C
AC
D002110:Caffeine / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003543:Cysteamine / Q000494:pharmacology*; D004249:DNA Damage; D004260:DNA Repair; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured
D002110:Caffeine; D003543:Cysteamine