Carcinogenicity of N-nitrosamines related to N-butyl-N-(4-hydroxybutyl)nitrosamine and N,N,-dibutylnitrosamine in ACI/N rats.
Carcinogenic effect of 14 N-nitrosamines related to N-butyl-N-(4-hydroxybutyl(nitrosamine (BBN) and N,N-dibutylnitrosamine (DBN) was studied in ACI/N male rats by administration in the drinking water. BBN homologs having methyl, ethyl, or pentyl group selectively induced urinary bladder tumors, but a homolog with tert-butyl group did not have any carcinogenic effect. N-Ethyl-N-(3-carboxypropyl)nitrosamine, the principal urinary metabolite of the ethyl homolog of BBN, did also induce bladder tumors selectively, thus providing an additional evidence that N-alkyl-N-(3-carboxypropyl)nitrosamines are responsible for the selective induction of bladder tumors by BBN homologs. N-Butyl-N-(carboxymethyl)nitrosamine and BBN analogs having 3-hydroxypropyl chain together with ethyl or butyl group were found to be noncarcinogenic. N-Propyl-N-butylnitrosamine and DBN induced hepatomas, but simultaneous development of esophageal tumors were observed only with the former. N-Butyl-N-(3-hydroxybutyl)nitrosamine, one of the principal metabolities of DNB, did not induce any  tumors, but its further transformation product, N-butyl-N-(3-oxobutyl)nitrosamine as well as N-butyl-N-(2-oxobutyl)nitrosamine, another metabolic intermediate of DBN, induced hepatomas. Possible correlation of structure and metabolism with organotropic carcinogenesis by N-N-dialkylnitrosamines is discussed, with special reference to selective induction of urinary bladder tumors.
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight; D002085:Butylhydroxybutylnitrosamine / Q000494:pharmacology; D002273:Carcinogens; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced; D008113:Liver Neoplasms / Q000139:chemically induced; D008297:Male; D009602:Nitrosamines / Q000494:pharmacology*; D051381:Rats; D011912:Rats, Inbred ACI; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced
D002273:Carcinogens; D009602:Nitrosamines; D002085:Butylhydroxybutylnitrosamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase