ETHANOL-MEDIATED PROMOTION OF ESOPHAGEAL CARCINOGENESIS - ASSOCIATIONWITH LIPID-PEROXIDATION AND CHANGES IN PHOSPHOLIPID FATTY-ACID PROFILE OF THE TARGET TISSUE

Ethanol consumption is a high risk factor for oesophageal carcinoma an d studies indicate that it acts as a promoter of N-nitrosomethylbenzyl amine (NMBzA)-induced oesophageal carcinogenesis. The studies describe d here indicate that ethanol-induced promotion was related with an inc rease in indices of lipid peroxidation in the target oesophageal tissu e and that such an increase was associated with significant changes in the fatty acid profile of phospholipids. Young Sprague-Dawley rats we re treated with NMBzA, 2.5 mg/kg body weight, three times a week for 3 weeks, and a week afterwards fed a 7% ethanolic diet that was continu ed until their death at 10 months. Cumulative ethane exhaled by rats w as measured a week before their death and was found to increase signif icantly with NMBzA treatment but more so when followed by ethanol cons umption. Cholesterol, phospholipids, and some indices of lipid peroxid ation were measured in the oesophagus and liver. Whereas the levels of cholesterol and phospholipids were not affected in control-fed rats w ith or without the NMBzA treatment, ethanol consumption by either the untreated or NMBzA-treated rats caused a significant increase in the t argeted oesophagus as well as the liver, the major site of ethanol and carcinogen metabolism Ethanol consumption also increased all the indi ces of lipid peroxidation, i.e, malondialdehyde, lipid fluorescence, d iene- and triene-conjugates; the largest increases were observed in ra ts that received both NMBzA and ethanol. A comparison of the fatty aci d profile of phospholipids from the oesophagus and liver indicated sig nificant alterations both with the NMBzA treatment and ethanol consump tion. However, the fatty acid profile with regard to its peroxidabilit y was significantly modified only with ethanol consumption and only in the aesophagus of the NMBzA-treated or untreated rats. Also, hepatic phospholipids showed a substantial increase in linolenate and no chang e in arachidonate, but the oesophageal phospholipids exhibited a prono unced increase in the levels of C18:3, C20:2, C20:3, C20:3' and C22:6 with a significant increase in arachidonate when use of ethanol follow ed the NMBzA treatment, suggesting a disorder in lipid and eicosanoid metabolism. We propose that ethanol may promote carcinogenesis through excessive cell proliferation induced by disordered lipid and eicosano id metabolism that may cause a selective outgrowth of the initiated ce lls.