title: Substitution of equally carcinogenic UV-A for UV-B irradiations lowers epidermal thymine dimer levels during skin cancer induction in hairless mice.
abstract: Cyclobutane pyrimidine dimers (CPD) are the predominant DNA lesions induced by UV-B radiation, among these lesions thymine dimers are most frequent. Although UV-A radiation may also induce CPD, it has been found that equally cytotoxic or equally mutagenic UV-A and UV-B doses do not induce equal amounts of CPD, indicating that other DNA adducts contribute to the UV-A effects. Thus far it has not been established whether this finding can be extrapolated and also holds true for the more complex biological endpoint of skin cancer. Therefore, we compared thymine 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 would react similarly regarding the occurrences of carcinomas, with a median latency time of 170 +/- 10 days. After 50, 106 and 151 days of irradiation eight hairless mice (SKH:HR1) from both groups were euthanized 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. Both in total epidermal cell populations and in subpopulations of replicating epidermal cells thymine dimer levels were significantly lower in the UV-A/B combination group than in the UV-B group (0.010 < P < 0.025 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.
authors.affiliation: Institute of Dermatology, University Hospital Utrecht, Utrecht University, The Netherlands.
authors.forename: R J
authors.initials: RJ
authors.lastname: Berg
authors.forename: A
authors.initials: A
authors.lastname: de Laat
authors.forename: L
authors.initials: L
authors.lastname: Roza
authors.forename: J C
authors.initials: JC
authors.lastname: van der Leun
authors.forename: F R
authors.initials: FR
authors.lastname: de Gruijl
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000528:radiation effects; D003609:Dactinomycin / Q000031:analogs & derivatives; D004817:Epidermis / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D051379:Mice; D008812:Mice, Hairless; D009381:Neoplasms, Radiation-Induced / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D011740:Pyrimidine Dimers / Q000032:analysis*; D012867:Skin / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014466:Ultraviolet Rays
chemical_list: D005456:Fluorescent Dyes; D011740:Pyrimidine Dimers; D003609:Dactinomycin; C025942:7-aminoactinomycin D; D016650:Fluorescein-5-isothiocyanate