Elevated levels of prostaglandin E 2 in the liver of rats fed a choline deficient diet: possible involvement in liver tumor promotion

Abstract

The effect of feeding a choline deficient (CD) diet, an efficient liver tumor promoting regimen, on the prostaglandin metabolism in the liver of male Sprague-Dawley rats was investigated. The possible biological significance of the alteration was examined using hypolipidemic peroxisome proliferators and modifiers of prostaglandin metabolism such as indomethacin and menhaden oil in the short term assay of the induction of enzyme altered foci in the liver. A CD diet, when fed for 10–30 days, induced 2–2.5· times increases in the levels of prostaglandin E 2 (PGE 2) in the liver, while the hypolipidemic peroxisome proliferators, 4-chloro-6(2,3-xylidino) pyrimidinylthio(N-hydroxyethyl)-acetamide (BR93l) and di(2-ethylhexyl)-phthalate (DEHP), markedly reduced the levels of this metabolite. The addition of BR93l or indomethacin to a CD diet suppressed the diet-induced elevations of PGE 2 and a substitution of fats in a CD diet with menhaden oil had the same effect. Furthermore, both indomethacin and menhaden oil added to a CD diet suppressed the induction of γ-glutamyltranspeptidase positive hepatocyte foci in the liver of rats initiated with a single dose of diethylnitrosamine after 8 weeks of the dietary promotion. The results suggest that altered prostaglandin metabolism may be involved in the liver tumor promoting effect of a CD diet.