Reduction of rat liver carcinogenicity of 4-nitrosomorpholine by alpha-deuterium substitution.
Groups of 30 males Sprague-Dawley rats were given 4-nitrosomorpholine-3,3,5,5-d in their drinking water at concentrations of 0.35 and 0.07 X 10(-3) M for 30 weeks. Two similar groups of rats were simultaneously given unlabeled 4-nitrosomorpholine (NM) at the same malar concentrations; all animals were observed throughout their lives. Those receiving the alpha-deuterium-labeled compound had significantly fewer liver tumors than did the corresponding animals receiving the unlabeled compound. The difference in potency appeared to be at least fivefold, a magnitude consistent with a primary kinetic isotope effect on the carcinogenic action of NM. Thus breakage of a bond linking a hydrogen (deuterium) atom with carbon adjacent to the nitrosamino function may be involved in a rate-limiting step of carcinogenesis by NM.
D000818:Animals; D002273:Carcinogens; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced*; D055598:Chemical Phenomena; D002621:Chemistry; D003903:Deuterium; D006390:Hemangioendothelioma / Q000139:chemically induced; D008113:Liver Neoplasms / Q000139:chemically induced*; D008297:Male; D009025:Morpholines / Q000633:toxicity*; D009374:Neoplasms, Experimental / Q000139:chemically induced; D051381:Rats
D002273:Carcinogens; D009025:Morpholines; D003903:Deuterium