Model Studies on the in Vitro Activation of c-Ha-ras Protooncogene by Dietary Components
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 cells2,3. 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.
KeywordsChemical Carcinogen Single Base Pair B6C3F1 Mouse Base Pair Mismatch Ultimate Carcinogen
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- 6.R. W. Wiseman, B. C. Stewart, D. Grenier, E. C. Miller and J. A. Miller, Characterization of c-Ha-ras proto-oncogene mutations in chemically induced hepatomas of B6C3F1 mouse, Proc. Amer. Assoc. Canc. Res. 28:147 (1987).Google Scholar