Carcinogenicity of methylated derivatives of N-nitrosodiethylamine and related compounds in Sprague-Dawley rats.
Five nitrosamines, which can be considered alkyl derivatives of N-nitrosodiethylamine, were tested for carcinogenicity by administration to Sprague-Dawley rats in drinking water at approximately equimolar concentrations. N-Nitrosodi-n-propylamine was a potent carcinogen but less so than N-nitrosodiethylamine and gave the same spectrum of tumors. N-Nitrosodiisopropylamine was very much weaker than N-nitrosodiethylamine and induced only tumors of the nasal turbinates in significant incidence. At the doses given, neither N-nitrosodiisobutylamine nor N-nitrosodi-sec-butylamine was significantly carcinogenic. In contrast, the cyclic nitrosamine N-nitrosohexamethyleneimine was equally potent with N-nitrosodiethylamine and gave the same spectrum of tumors in liver, esophagus, and nasal turbinates. The results support the concept that oxidation at the alpha carbon atom of nitrosamines is a significant step in carcinogenesis.
D000818:Animals; D002273:Carcinogens; D004052:Diethylnitrosamine / Q000031:analogs & derivatives / Q000633:toxicity*; D004938:Esophageal Neoplasms / Q000139:chemically induced; D005260:Female; D008113:Liver Neoplasms / Q000139:chemically induced; D008297:Male; D008745:Methylation; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D009602:Nitrosamines / Q000633:toxicity*; D009669:Nose Neoplasms / Q000139:chemically induced; D051381:Rats; D013329:Structure-Activity Relationship
D002273:Carcinogens; D009602:Nitrosamines; D004052:Diethylnitrosamine