Mutation induction with UVB in mouse skin epidermis is suppressed in acute high-dose exposure

The time and dose dependence of ultraviolet B (UVB)-induced mutant frequency (MF) in skin epidermis and dermis was studied with transgenic Muta(TM) mice harboring lambdagt10lacZ shuttle vector. Mutants of the lacZ transgene appearing in these tissues after 0.5 kJ/m(2) UVB irradiation were fully expressed in 3-7 days, and the frequencies of those fully expressed mutants were maintained for at least the following 3 weeks. These fully expressed MFs increased dose-dependently, with the initial slope for the epidermis four times larger than that for dermis. Surprisingly, in epidermis, an inhibition of the dose-dependent mutation induction was evident after irradiation above 0.5 kJ/m(2) UVB, lowering the increment more than eight-fold, while such suppression was not observed in dermis. This anticarcinogenic epidermal response disappeared with dose fractionation when the fractions were delivered at 4-week intervals, but not when delivered every day, showing that the induced mutation suppression is maintained under continual repetitive exposure, without which it expires within 4 weeks. These results suggest that repetition of heavy sun exposure at long intervals, e.g. recreational sunbathing every summer, is more likely to cause skin cancer than every day continual exposure even if the total UV doses are the same. (C) 2002 Elsevier Science B.V. All rights reserved.