Low incidence of p53 mutations in UVA (365-nm)-induced skin tumors in hairless mice.
Mutations with clear "UVB fingerprints" have been observed in the p53 gene of human nonmelanoma skin tumors and of experimentally UVB-induced murine skin tumors. Although UVA (315-400 nm) radiation is also a complete carcinogen, its contribution to sunlight-induced mutagenesis remains poorly characterized. There is experimental evidence that the production of reactive oxygen species plays a more dominant role with long-wave UVA than with UVB radiation. We have induced skin tumors (n = 42) in hairless SKH:HR1 mice (n = 14) by daily exposure to long-wave UVA (365-nm) radiation. The incidence of p53 alterations in these tumors is low compared to UVB-induced tumors; positive staining for the p53 protein was observed in only 50% of the tumors, and less than 15% of the tumors showed a mutation in one of the exons 5, 7, or 8 of the p53 gene. The pattern of p53 staining was more irregular and less dense compared to UVB, and the mutations (all C-->T) were mainly (six of seven) located at codon 267. Besides a general p53 hotspot, this codon is also the main hotspot for UVB-induced skin tumors in these mice. No mutations specific for UVA, ie., mutations specific for reactive oxygen species, could be detected.
van Kranen
H J
HJ
Laboratory of Health Effects Research, National Institute of Public Health and the Environment, BA Bilthoven, the Netherlands.
de Laat
A
A
van de Ven
J
J
Wester
P W
PW
de Vries
A
A
Berg
R J
RJ
van Kreijl
C F
CF
de Gruijl
F R
FR
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D016158:Genes, p53 / Q000528:radiation effects; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D009381:Neoplasms, Radiation-Induced; D010212:Papilloma / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics*; D014466:Ultraviolet Rays