Oncogene activation in experimental carcinogenesis: the role of carcinogen and tissue specificity.
Techniques of molecular biology have been used to determine the relationship of cellular oncogenes to mechanisms of experimental carcinogenesis. Model systems involving three direct-acting alkylating carcinogens, two organ sites, and two species have been employed to elucidate the relationships between carcinogenic etiology, tissue specificity, and activation of known and novel oncogenes. Dimethylcarbamyl chloride, a reactive acylating agent, induces tumors of both the rat nasal mucosa and mouse skin whose DNA is devoid of NIH 3T3 transforming activity. Beta-propiolactone-induced rat nasal carcinomas contain a novel oncogene, 6 to 9 kb in size, whereas a mouse skin carcinoma induced by this agent possesses an H-ras oncogene activated by a 61st codon A to T transversion mutation. The novel oncogene activated in rat nasal tumors induced by beta-propiolactone is distinct from one found in methylmethane sulfonate-induced tumors. The implications of these findings for understanding how oncogenes fit into general mechanism of carcinogenesis are discussed.
Garte
S J
SJ
Department of Environmental Medicine, New York University Medical Center, NY 10016.
Hochwalt
A E
AE
D000818:Animals; D002219:Carbamates / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D051379:Mice; D009669:Nose Neoplasms / Q000139:chemically induced / Q000235:genetics; D009857:Oncogenes / Q000187:drug effects*; D009928:Organ Specificity; D011420:Propiolactone / Q000494:pharmacology; D051381:Rats; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics
D002219:Carbamates; D002273:Carcinogens; C001036:dimethylcarbamyl chloride; D011420:Propiolactone; D008741:Methyl Methanesulfonate