Dl. Mitchell et al., Effects of chronic low-dose ultraviolet B radiation on DNA damage and repair in mouse skin, CANCER RES, 59(12), 1999, pp. 2875-2884
Chronic exposure to sunlight causes skin cancer in humans, yet little is kn
own about how habitual exposure to low doses of ultraviolet B radiation (UV
B) affects DNA damage in the skin. We treated Skh-1 hairless mice with dail
y doses of suberythemal UVB for 40 days and analyzed the amount and distrib
ution of DNA photodamage using RIAs and immunofluorescence micrography. We
found that DNA damage accumulated in mouse skin as a result of chronic irra
diation and that this damage persisted in the dermis and epidermis for seve
ral weeks after the chronic treatment was terminated. Although the persiste
nt damage was evenly distributed throughout the dermis, it remained in the
epidermis as a small number of heavily damaged cells at the dermal-epiderma
l boundary. Rates of DNA damage induction and repair were determined at dif
ferent times over the course of chronic treatment in response to a higher c
hallenge dose of UVB light. The amount of damage induced by the challenge d
ose increased in response to chronic exposure, and excision repair of cyclo
butane pyrimidine dimers and pyrimidine(6-4)pyrimidone dimers was significa
ntly reduced. The sensitization of mouse epidermal DNA to photoproduct indu
ction, the reduction in excision repair, and the accumulation of nonrepaira
ble DNA damage in the dermis and epidermis suggest that chronic low-dose ex
posure to sunlight may significantly enhance the predisposition of mammalia
n skin to sunlight-induced carcinogenesis.