PREFERENTIAL FORMATION OF BENZO[A]PYRENE ADDUCTS AT LUNG-CANCER MUTATIONAL HOTSPOTS IN P53

Cigarette smoke carcinogens such as benzo[a]pyrene are implicated in t he development of lung cancer. The distribution of benzo[a]pyrene diol epoxide (BPDE) adducts along exons of the P53 gene in BPDE-treated He La cells and bronchial epithelial cells was mapped at nucleotide resol ution. Strong and selective adduct formation occurred at guanine posit ions in codons 157, 248, and 273. These same positions are the major m utational hotspots in human lung cancers. Thus, targeted adduct format ion rather than phenotypic selection appears to shape the P53 mutation al spectrum in lung cancer. These results provide a direct etiological link between a defined chemical carcinogen and human cancer.