Sunlight and carcinogenesis: expression of p53 and pyrimidine dimers in human skin following UVA I, UVA I + II and solar simulating radiations.
DNA damage by UV radiation plays an essential role in skin cancer induction. We report that even sub-erythemal doses of solar simulating radiation, are capable of inducing substantial nuclear damage, namely pyrimidine dimers and p53 induction in human skin in situ. The quantity and distribution of p53 induced in human skin by UV radiation depended highly on the waveband and dose of UV used. Solar simulating radiation induced very high levels of p53 throughout all layers in epidermal keratinocytes 24 hr following an erythemal dose (230+/-15.9/1000 cells), and the induction followed a dose response. Following UVA I + II and UVA I radiations, p53 expression was approximately half of that seen with equivalent biological doses of solar simulating radiation (63.5+/-28.5 and 103+/-15.9, respectively). Expression of p53 was seen in basal cell keratinocytes at lower doses of UVA, but all layers of the epidermis were affected at higher doses. Pyrimidine dimer induction, however, was seen to be the same for equivalent biological doses of UVA I, UVA I + II and solar simulating radiations, which coincides with previous findings that pyrimidine dimers initiate the erythemal response and are implicated in skin carcinogenesis. When equivalent biological doses of pure UVA are used with no UVB contamination, significant nuclear alterations occur in human skin in situ, which can approach those seen with UVB radiation. Our results suggest that DNA damage assessed in vivo by immunohistochemistry could provide a very sensitive endpoint for determining the efficacy of protective measures, such as sunscreens or protective clothing, against both UVB- and UVA-induced damage in human skin.
Burren
R
R
Department of Dermatology, University Hospital, Lausanne, Switzerland.
Scaletta
C
C
Frenk
E
E
Panizzon
R G
RG
Applegate
L A
LA
D000328:Adult; D000906:Antibodies; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D015870:Gene Expression; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011740:Pyrimidine Dimers / Q000096:biosynthesis*; D012867:Skin / Q000378:metabolism*; D012878:Skin Neoplasms / Q000209:etiology* / Q000378:metabolism; D013472:Sunlight / Q000009:adverse effects*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000276:immunology; D014466:Ultraviolet Rays
D000906:Antibodies; D011740:Pyrimidine Dimers; D016159:Tumor Suppressor Protein p53; D004247:DNA