Ultraviolet-light induced p53 mutational spectrum in yeast is indistinguishable from p53 mutations in human skin cancer.
Ultraviolet (UV) light has been associated with the development of human non-melanoma skin cancers (NMSC). Such cancers often exhibit mutations in the p53 tumour suppressor gene. In order to determine the UV-induced p53 mutation spectrum, a yeast expression vector that harbours a human wild-type p53 cDNA was UV-irradiated in vitro and transfected into a yeast strain that contained the ADE2 gene regulated by a p53-responsive promoter. Forty-five mutant clones contained 51 mutations. Seven mutations were tandem base pair substitutions, four of which being CC-->TT, hallmark mutations of UV mutagenesis. Eighty percent (41/51) of the mutations were single or non-tandem base pair substitutions, the majority of which (27/41) were C-->T transitions. Ninety-five percent of such mutations occurred at dipyrimidine sites. Through a rigorous statistical test, the UV-induced p53 mutation spectrum appears to differ significantly (P < 0.008) from the one induced by the antineoplastic drug chloroethyl-cyclohexyl-nitrosourea, and to be indistinguishable from the one observed in NMSC (P = 0.4). These results demonstrate that the assay allows the determination of carcinogen-specific p53 mutation fingerprints and represents a new tool for molecular epidemiology.
Inga
A
A
CSTA-Mutagenesis Laboratory, National Institute for Research on Cancer (IST), Largo R. Benzi, Genova, Italy.
Scott
G
G
Monti
P
P
Aprile
A
A
Abbondandolo
A
A
Burns
P A
PA
Fronza
G
G
D018076:DNA, Complementary / Q000528:radiation effects; D016158:Genes, p53; D006801:Humans; D008545:Melanoma / Q000209:etiology / Q000235:genetics*; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014466:Ultraviolet Rays
D018076:DNA, Complementary; D016159:Tumor Suppressor Protein p53