Activation of H-ras-1 oncogenes by chemical carcinogens

Efforts aimed at establishing the role of ras oncogenes in human neoplasia are complicated by the unknown etiology of most human cancers and the impossibility of experimental manipulations. In animal model systems that closely parallel human neoplasia, we have shown that transforming ras genes can be reproducibly identified in mammary carcinomas of rats induced by the chemical carcinogen nitroso-methyl-urea (NMU). In this article, we discuss the specific activation of the H-ras-1 locus in mammary carcinomas of rats induced by different chemical carcinogens. We provide experimental evidence that the mutagenic activity of the carcinogens utilized is directly responsible for the malignant activation of the H-ras-1 oncogenes. 47 refs., 3 figs., 3 tabs