Carcinogenicity tests of acetoxymethylphenylnitrosamine and benzenediazonium tetrafluoroborate in Syrian hamsters.
The metabolic activation of the esophageal carcinogen methylphenylnitrosamine (MPhN) via alpha-hydroxylation to hydroxymethylphenylnitrosamine (HO-MPhN) should afford benzenediazonium ion (BDI) as the ultimate electrophilic metabolite. To determine if this proposed activation pathway is accurate, BDI, as its tetrafluoroborate (BF4) salt, was tested by chronic subcutaneous injection and gavage in Syrian golden hamsters. Acetoxymethylphenylnitrosamine (AMPhN), which is rapidly hydrolyzed to HO-MPhN in vivo, was similarly tested by s.c. injection. AMPhN was weakly carcinogenic, while BDI-BF4 did not induce a significant tumor incidence by subcutaneous administration. When orally administered, BDI was inactive. Both AMPhN and BDI-BF4 were mutagenic only in Salmonella typhimurium strain TA1537 without enzymic activation. The parent nitrosamine, MPhN was also mutagenic in TA1537, but only with enzymic activation. The mechanistic and environmental significance of these results are discussed.
D000284:Administration, Oral; D000818:Animals; D002273:Carcinogens; D006224:Cricetinae; D003979:Diazonium Compounds / Q000378:metabolism / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D007279:Injections, Subcutaneous; D007928:Lethal Dose 50; D009152:Mutagenicity Tests; D009374:Neoplasms, Experimental / Q000139:chemically induced; D009602:Nitrosamines / Q000378:metabolism / Q000633:toxicity*
D002273:Carcinogens; D003979:Diazonium Compounds; D009602:Nitrosamines; C035176:benzenediazonium; C035175:acetoxymethylphenylnitrosamine