Epidermal proliferation but not quantity of DNA photodamage is correlated with UV-induced mouse skin carcinogenesis.
The hairless SKH-1 mouse strain has a higher skin tumor incidence, shorter tumor latency, and higher tumor yield in response to ultraviolet (UV) irradiation than the SENCAR strain. In this study we assessed the differences in UV susceptibility of both strains by measuring DNA photodamage and epidermal proliferation after one UV treatment and after 1, 3, 6, and 9 wk of chronic UV irradiation. Induction rates for cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts [(6-4) PDs] were significantly greater in the SKH-1 strain than the SENCAR strain, but no strain differences in repair kinetics were detected for CPDs or (6-4) PDs. With chronic UV exposure we observed the following: (i) there was an equal amount of DNA photodamage in both strains; (ii) the number of (6-4) PDs was significantly greater than the CPDs after 6 wk; (iii) there were a significantly greater number of epidermal cells (1.5-fold increase) in the SKH-1 strain; (iv) the number of cycling cells, as measured by 5-bromo-2'-deoxyuridine (BrdU), were located both basally and suprabasally and were significantly greater in the SKH-1 strain; and (v) the number of cells immunoreactive to p53 was equivalent in both strains, but immunoreactive cells were located suprabasally in the SKH-1 strain after 9 wk of UV. These results show that the etiologic role of UV in tumorigenesis is dependent on events other than the amount of DNA photodamage in mouse epidermis.
Berton
T R
TR
Division of Nutritional Sciences, University of Texas at Austin, U.S.A.
Mitchell
D L
DL
Fischer
S M
SM
Locniskar
M F
MF
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division / Q000528:radiation effects; D004247:DNA / Q000096:biosynthesis; D004249:DNA Damage / Q000528:radiation effects*; D005260:Female; D015870:Gene Expression / Q000528:radiation effects; D016158:Genes, p53 / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006965:Hyperplasia / Q000201:enzymology; D051379:Mice; D008812:Mice, Hairless; D018632:Mice, Inbred SENCAR; D009381:Neoplasms, Radiation-Induced / Q000209:etiology; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011740:Pyrimidine Dimers / Q000032:analysis; D012867:Skin / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000209:etiology*; D014466:Ultraviolet Rays
D011740:Pyrimidine Dimers; D004247:DNA; D009955:Ornithine Decarboxylase; D001973:Bromodeoxyuridine