Histopathological and radioautographical studies on the forestomach of F344 rats treated with butylated hydroxyanisole and related chemicals

Abstract

Butylated hydroxyanisole, when fed to male Fischer 344 rats for periods of 9 days or more, led to forestomach epithelial cell necrosis and regeneration. Both the induced proliferation and the histopathological changes were considerably more prevalent in the prefundic region of the forestomach than in the mid-region. Using [Me-3H]thymidine, a specific DNA precursor, and radioautography it was shown that the effect of the antioxidant was apparently threshold at 0.25% in the diet after both 9 days and 3 months of treatment and that the proliferation was dependent on the continuous presence of the antioxidant in the diet at 3 and 6 months. Some other phenols and acids were investigated after 9-27 days' feeding; most induced some degree of epithelial cell proliferation in the rat forestomach, although some had a greater effect on the mid-region than on the prefundic region. These observations are discussed in terms of the likely relevance of butylated hydroxyanisole-induced forestomach tumours to the possibility that the antioxidant may lead to cancer in humans exposed to lower levels in their diet.