Differences between isoamyl alcohol and ethanol on the metabolism and DNA ethylation of N-nitrosodiethylamine in the rat.
The association between alcohol consumption and esophageal cancer is particularly marked in Northern France where an apple brandy, Calvados, is drunk. Calvados contains branched chain alcohols such as isoamyl alcohol (IAA) and it has been suggested that these play a particular role in the etiology of the cancer. In this study the effect of IAA, alone or with ethanol, on the ethylation of DNA by N-nitrosodiethylamine was evaluated in living rats, and the effect of IAA on the metabolism of N-nitrosodiethylamine by rat liver microsomes or esophageal epithelium was measured. As previously reported co-administration of ethanol increases the ethylation of esophageal DNA by the nitrosamine by almost 2-fold, but IAA did not alter the proportion of DNA ethylation between liver and esophagus. When both alcohols were given together with the nitrosamine, the alteration on DNA ethylation produced by ethanol remained unchanged. Different from ethanol, IAA inhibited NDEA metabolism catalyzed not only by rat liver microsomes (K(i)=0.42 mM), but also by esophageal epithelium (K(i)=0.52 mM), thus possessing an affinity also for the esophageal NDEA metabolizing P450.
Ribeiro Pinto
L F
LF
Departmento de Bioquímica, IBRAG, Universidade do Estado do Rio de Janeiro, Av. 28 de Setembro, 87, fundos 4 andar, Vila Isabel, 20551-013, Rio de Janeiro, Brazil. fpinto@uerj.br
D000478:Alkylation; D000818:Animals; D002273:Carcinogens / Q000378:metabolism* / Q000633:toxicity*; D002492:Central Nervous System Depressants / Q000633:toxicity*; D004247:DNA / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D004052:Diethylnitrosamine / Q000378:metabolism* / Q000633:toxicity*; D004947:Esophagus / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D000439:Pentanols / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002273:Carcinogens; D002492:Central Nervous System Depressants; D000439:Pentanols; D004052:Diethylnitrosamine; D000431:Ethanol; D004247:DNA; C029683:isopentyl alcohol