TY - JOUR
T1 - Ultraviolet-light induced p53 mutational spectrum in yeast is indistinguishable from p53 mutations in human skin cancer
AU - Inga, Alberto
AU - Scott, Gina
AU - Monti, Paola
AU - Aprile, Anna
AU - Abbondandolo, Angelo
AU - Burns, Philip A.
AU - Fronza, Gilberto
PY - 1998/5
Y1 - 1998/5
N2 - 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 chloroethylcyclohexyl-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.
AB - 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 chloroethylcyclohexyl-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.
UR - http://www.scopus.com/inward/record.url?scp=0031844522&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031844522&partnerID=8YFLogxK
U2 - 10.1093/carcin/19.5.741
DO - 10.1093/carcin/19.5.741
M3 - Article
C2 - 9635858
AN - SCOPUS:0031844522
VL - 19
SP - 741
EP - 746
JO - Carcinogenesis
JF - Carcinogenesis
SN - 0143-3334
IS - 5
ER -