Carcinogenesis in rats by asymmetric nitrosamines containing an allyl group.
Four asymmetric nitrosamines containing 1 allyl group were administered to rats in drinking water to aid in understanding the failure of nitrosodiallylamine ( NDAA ) to induce tumors in rats. Three of the compounds were given at equimolar doses, the fourth at somewhat lower dose. All four nitrosamines induced tumors of the esophagus and/or nasal cavity. Nitrosoallylethanolamine (NAE) induced a 30% incidence of hepatocellular carcinomas, while nitrosoallyl -2- hydroxypropylamine induced 70% hepatocellular carcinomas and a much lower dose of nitrosoallyl -2- oxopropylamine induced 80% of hepatocellular carcinomas, several of which metastasized. Nitrosoallyl -2,3- dihydroxypropylamine , which increased the mortality from tumors much more than the other compounds, failed to induce tumors in the liver, but induced a high incidence (85%) of tumors of the esophagus. The conclusion is that the allyl group is not metabolically inert, but that its presence in these molecules modifies their metabolism so as to give rise to tumors in a variety of organs. It does not seem that formation of an allylating agent is the common mechanism of carcinogenesis by these compounds.
D000498:Allyl Compounds / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000633:toxicity*; D004938:Esophageal Neoplasms / Q000139:chemically induced; D005260:Female; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D009296:Nasal Cavity; D009602:Nitrosamines / Q000378:metabolism / Q000633:toxicity*; D009669:Nose Neoplasms / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000498:Allyl Compounds; D002273:Carcinogens; D009602:Nitrosamines; C015125:diallylnitrosamine; C041199:N-nitrosoallyl-2,3-dihydroxypropylamine; C041196:N-nitroso-N-allyl-N-ethanolamine; C041197:N-nitroso-2-hydroxypropylamine; C041198:N-nitrosallyl-2-oxopropylamine