Model Studies on the in Vitro Activation of c-Ha-ras Protooncogene by Dietary Components

Abstract

Evidence for the activation of ras protooncogenes by chemical carcinogens is provided both by the reproducible activation observed in chemically-induced animal tumors (reviewed in 1) and by our demonstration that in vitro modification of ras protooncogenes with ultimate carcinogens results in transformed foci on transfection into NIH3T3 cells^2,3. In the present study, transforming oncogenes have been generated by the in vitro modification of plasmid containing human c-Ha-ras with the model ultimate carcinogens 3-N, N-acetoxyacetylamino-4,6-dimethyl-dipyrido[1,2-a:3′,2′-d]imidazole (N-AcO-AGlu-P-3) and 1′-acetoxysafrole (AcO-safrole). The mutations produced have been analyzed by selective amplification of the regions surrounding codons 12 and 61 and subsequent oligonucleotide hybridization.