Metabolism of N-nitrosodimethylamine and N-nitrosomethylbenzylamine in domestic fowls: DNA alkylation and potential target sites for carcinogenicity.
The metabolism and reaction with DNA of N-nitrosodimethylamine (NDMA) and N-nitrosomethylbenzylamine (NMBzA) were investigated in chickens. These nitrosamines have been identified in a typical diet consumed in northern Chinese provinces with a high incidence of oesophageal cancer in both, humans and domestic fowls. Following i.m. or oral administration of the 14C-methyl labeled nitroso compounds (16.5 mumol/kg) less than 10% of the total radioactivity was exhaled as 14CO2 within 24 hr. DNA alkylation in chicken tissues was generally low, with highest values in liver (approximately 30 mumol N7-methylguanine/mol guanine) and kidney. In the gastrointestinal tract, concentrations of methylpurines were close to the limit of detection. After oral administration of NMBzA the reaction with DNA was more extensive, in particular in the diverticulum (crop), where N7-methylguanine and 0(6)-methylguanine amounted to 32 and 3.5 mumol/mol guanine, respectively. These values are more than 10-fold lower than those produced by a similar dose in rats, i.e. a species in which NMBzA induces a high incidence of oesophageal carcinomas. The low capacity of the chicken mucosa to bioactivate NDMA and NMBzA argues against these nitrosamines as agents responsible for oesophageal cancer in high risk areas.
D000478:Alkylation; D000818:Animals; D001944:Breath Tests; D002245:Carbon Dioxide / Q000032:analysis; D002645:Chickens / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives* / Q000378:metabolism*; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D008745:Methylation; D009152:Mutagenicity Tests; D013997:Time Factors
D002245:Carbon Dioxide; D006147:Guanine; C008450:7-methylguanine; D004247:DNA; C014707:nitrosobenzylmethylamine; D004128:Dimethylnitrosamine