SUBSTITUTION OF EQUALLY CARCINOGENIC UV-A FOR UV-B IRRADIATIONS LOWERS EPIDERMAL THYMINE DIMER LEVELS DURING SKIN-CANCER INDUCTION IN HAIRLESS MICE

Cyclobutane pyrimidine dimers (CPD) are the predominant DNA lesions in duced by UV-B radiation, among these lesions thymine dimers are most f requent, Although UV-A radiation may also induce CPD, it has been foun d that equally cytotoxic or equally mutagenic UV-A and UV-B doses do n ot induce equal amounts of CPD, indicating that other DNA adducts cont ribute to the UV-A effects. Thus far it has not been established wheth er this finding can be extrapolated and also holds true for the more c omplex biological endpoint of skin cancer. Therefore, we compared thym ine dimer levels during skin cancer induction by combined UV-A and UV- B daily exposures with the levels from equally carcinogenic daily UV-B exposures. From control experiments it was known that both groups wou ld react similarly regarding the occurrences of carcinomas, with a med ian latency time of 170 +/- 10 days. After 50, 106 and 151 days of irr adiation eight hairless mice (SKH:HR1) from both groups were euthanize d and thymine dimers in epidermal cell suspensions were quantified by flow cytometry. Staining on DNA content enabled us to quantify thymine dimers in G0/G1-phase, in S-phase and in G2M-phase subpopulations. Bo th in total epidermal cell populations and in subpopulations of replic ating epidermal cells thymine dimer levels were significantly lower in the UV-A/B combination group than in the UV-B group (0.010 < P < 0.02 5 and P < 0.005 respectively). This indicates that the carcinogenicity of UV-A relative to that of UV-B is not properly measured by thymine dimers and that other DNA lesions than CPD, for example, from reactive oxygen species, are likely to contribute to UV-A carcinogenicity.