Combined effects of butylated hydroxyanisole and other antioxidants in induction of forestomach lesions in rats.

The possibility that changes in the forestomach of rats induced by butylated hydroxyanisole (BHA) are caused by inductions of free radicals and their reactions with macromolecules was examined. Groups of five male F344 rats were pretreated with 1% alpha-tocopherol, 1% ellagic acid, 1% propyl gallate, 0.25% ethoxyquin, 0.5% glutathione, 1% sodium L-ascorbate or 1% 3,3'-thiodipropionic acid for 1 week, then treated with the same antioxidant plus 1% BHA for 1 week, and then killed. Histological examination showed that BHA induced epithelial hyperplasia of the forestomach. This induction of hyperplasia was not inhibited, but increased by the antioxidants, particularly propyl gallate and ethoxyquin. Thus the induction of hyperplasia by BHA may not be related to a free radical reaction.