[Activation of oncogenes by chemical modification with carcinogens]

This article reviews the chemical modification of DNA (mainly proto-Ha-ras sequence) which causes mutation and induction of transforming activity. An initial chemical event caused by chemical carcinogens is modification of DNA with metabolically activated carcinogens. The chemical modification of DNA is thought to result in activation of oncogenes by mutation or reconstruction. The activated transforming oncogenes (mainly of the ras family, by point mutation) have been found in tumors induced by diverse carcinogens in vivo (reviewed briefly). Recently, results establishing that chemical modification of proto-oncogenes with carcinogens, such as benz (a) pyrene, acetylaminofluorene, Glu-P-1, 4NQO, and aflatoxin B1, induces transforming activity of the gene when transfected into NIH3T3 cells have been reported. The mechanism of activation of proto-Ha-ras by chemical modification has been investigated by RFLP (restriction fragment length polymorphism) assay and/or Southern blot analysis using synthetic oligonucleotides. Point mutations at codon 12 or 61 have been found. The correlation between the established chemistry of chemical modification of DNA with diverse carcinogens and activation of proto-oncogenes is discussed.