Effects of chronic low-dose ultraviolet B radiation on DNA damage and repair in mouse skin.
Chronic exposure to sunlight causes skin cancer in humans, yet little is known about how habitual exposure to low doses of ultraviolet B radiation (UVB) affects DNA damage in the skin. We treated Skh-1 hairless mice with daily doses of suberythemal UVB for 40 days and analyzed the amount and distribution of DNA photodamage using RIAs and immunofluorescence micrography. We found that DNA damage accumulated in mouse skin as a result of chronic irradiation and that this damage persisted in the dermis and epidermis for several weeks after the chronic treatment was terminated. Although the persistent damage was evenly distributed throughout the dermis, it remained in the epidermis as a small number of heavily damaged cells at the dermal-epidermal boundary. Rates of DNA damage induction and repair were determined at different times over the course of chronic treatment in response to a higher challenge dose of UVB light. The amount of damage induced by the challenge dose increased in response to chronic exposure, and excision repair of cyclobutane pyrimidine dimers and pyrimidine(6-4)pyrimidone dimers was significantly reduced. The sensitization of mouse epidermal DNA to photoproduct induction, the reduction in excision repair, and the accumulation of nonrepairable DNA damage in the dermis and epidermis suggest that chronic low-dose exposure to sunlight may significantly enhance the predisposition of mammalian skin to sunlight-induced carcinogenesis.
Mitchell
D L
DL
Department of Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Smithville 78957, USA. dmitch@io.com
Greinert
R
R
de Gruijl
F R
FR
Guikers
K L
KL
Breitbart
E W
EW
Byrom
M
M
Gallmeier
M M
MM
Lowery
M G
MG
Volkmer
B
B
D000818:Animals; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004260:DNA Repair / Q000528:radiation effects*; D005260:Female; D051379:Mice; D008819:Mice, Nude; D011829:Radiation Dosage; D012867:Skin / Q000473:pathology / Q000528:radiation effects*; D013472:Sunlight; D014466:Ultraviolet Rays
D004247:DNA