Potent inhibition of oesophageal metabolism of N-nitrosomethylbenzylamine, an oesophageal carcinogen, by higher alcohols present in alcoholic beverages.
The main cause of oesophageal cancer in western countries is consumption of alcoholic beverages, the degree of risk being much greater for certain spirits than for wine or beer. Risk shows a striking correlation with the content of higher alcohols in the drinks, although the alcohols per se have not been shown to be carcinogenic in experimental animals. To test the concept that higher alcohols modulate the oesophageal carcinogenicity of nitrosamines by altering their metabolism, we studied the effect of certain higher alcohols on the metabolism of N-nitrosomethylbenzylamine by rat oesophageal mucosal and liver microsomes. In oesophagus, the alcohols were 1000 times more inhibitory than ethanol, and in liver 100 times. This suggests that enhancement of carcinogenesis may not result from an effect on nitrosamine metabolism. Higher alcohols could act by increasing the rate of replication of cells already initiated for malignancy by previous exposure to nitrosamines. Intubation of 2-methylbutanol produces a very much greater increase in oesophageal basal-cell proliferation than does ethanol.
Craddock
V M
VM
MRC Toxicology Unit, Carshalton, Surrey, UK.
Henderson
A R
AR
D000434:Alcoholic Beverages; D000438:Alcohols / Q000494:pharmacology*; D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D004938:Esophageal Neoplasms / Q000139:chemically induced*; D004947:Esophagus / Q000378:metabolism*; D066298:In Vitro Techniques; D008861:Microsomes / Q000378:metabolism; D051381:Rats
D000438:Alcohols; D002273:Carcinogens; C014707:nitrosobenzylmethylamine; D004128:Dimethylnitrosamine