Effects of simultaneous treatment with various chemicals on BHA-induced development of rat forestomatch hyperplasia - complete inhibition by diethylmaletate in a 5-week feeding study

Abstract

Male F344 rats were administered phenobarbital, polychiorinated biphenyl (PCB), retinol acetate, indomethacin, 6-aminocaproic acid, dexamethazone (DEX) or diethylinaleate (DEM) for one week and then were treated with these chemicals plus butylated hydroxyanisole (BHA) for a further four weeks. Histopathologically, the incidence of BHA-induced fore-stomach hyperplasia was significantly lower in rats treated with PCB, DEX or DEM than in those treated with BHA alone. However, the inhibition by PCB and DEX was only partial and might have been due to decreased food intake. On the other hand, DEM completely inhibited the hyper plastic response to BHA at a dose of 0.25%, and even at lower doses it demonstrated significant inhibition without any decrease in body weight or food intake. The result that DEM, a tissue glutathione depleting agent, can inhibit BHA-associated forestomach hyperplasia strongly suggests that tissue glutathione may be intimately involved in the induction of forestomach hyperplasia by the antioxidant in rats.