Chemical structural effects in carcinogenesis by nitrosamines.
The effects of changes on chemical structure among groups of closely related nitrosamines on their carcinogenic effectiveness, including both potency and target organ specificity, have been examined by chronic oral administration of the nitrosamines to rats. The effects of deuterium substitution for hydrogen at various positions supports the concept that oxidation at the alpha position to the nitroso function is usually a key step in activation of carcinogenic nitrosamines. Methyl substituents at the alpha position reduce carcinogenic potency, supporting the same idea. A large number of derivatives of nitrosopiperidine have shown a large variation in carcinogenicity, not simply explained by differences in the relative rates of alpha oxidation. The effects of methyl substitution on the carcinogenicity of nitrosomorpholine and nitrosooxazolidine were opposite, although the unsubstituted compounds were of almost identical carcinogenic activity. The variations in the response of rats to a large series of nitrosodialkylamines indicated that they might be metabolized similarly, giving one or more common products which are the proximate carcinogens, and these biological effects can be related to the results of studies of the metabolism of these compounds in rats.
D000818:Animals; D001711:Biotransformation; D003903:Deuterium; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D009602:Nitrosamines / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D013329:Structure-Activity Relationship
D009602:Nitrosamines; C002743:N-nitrosopiperidine; D003903:Deuterium; C014711:1-nitrosopiperazine