Carcinogenesis, Vol 19, 741-746, Copyright © 1998 by Oxford University Press
A Inga, G Scott, P Monti, A Aprile, A Abbondandolo, PA Burns and G Fronza
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.
ARTICLES
Ultraviolet-light induced p53 mutational spectrum in yeast is indistinguishable from p53 mutations in human skin cancer
CSTA-Mutagenesis Laboratory, National Institute for Research on Cancer (IST), Largo R. Benzi, Genova, Italy.
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