Ethanol consumption is a high risk factor for oesophageal
carcinoma and studies indicate that it acts as a promoter of
N-nitrosomethylbenzylamine (
NMBzA)-induced oesophageal
carcinogenesis. The studies described here indicate that
ethanol-induced promotion was related with an increase in indices of lipid peroxidation in the target oesophageal tissue and that such an increase was associated with significant changes in the
fatty acid profile of
phospholipids. Young Sprague-Dawley rats were 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 continued until their death
at 10 months. Cumulative
ethane exhaled by rats was measured a week before their death and was found to increase significantly with
NMBzA treatment but more so when followed by
ethanol consumption.
Cholesterol,
phospholipids, and some indices of lipid peroxidation were measured in the oesophagus and liver. Whereas the levels of
cholesterol and
phospholipids were not affected in control-fed rats with or without the
NMBzA treatment,
ethanol consumption by either the untreated or
NMBzA-treated rats caused a significant increase in the targeted oesophagus as well as the liver, the major site of
ethanol and
carcinogen metabolism.
Ethanol consumption also increased all the indices of lipid peroxidation, i.e.
malondialdehyde,
lipid fluorescence, diene- and triene-conjugates; the largest increases were observed in rats that received both
NMBzA and
ethanol. A comparison of the
fatty acid profile of
phospholipids from the oesophagus and liver indicated significant alterations both with the
NMBzA treatment and
ethanol consumption. However, the
fatty acid profile with regard to its peroxidability was significantly modified only with
ethanol consumption and only in the oesophagus of the
NMBzA-treated or untreated rats. Also, hepatic
phospholipids showed a substantial increase in
linolenate and no change in arachidonate, but the oesophageal
phospholipids exhibited a pronounced 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 followed 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
eicosanoid metabolism that may cause a selective outgrowth of the initiated cells.