Enhancement of BHA-induced proliferative rat forestomach lesion development by simultaneous treatment with other antioxidants

Synergistic effects of butylated hydroxyanisole (BHA) and other antioxidants on induction of rat forestomach lesions were investigated. Groups of F344 male rats were treated with 1% BHA plus 0.7% butylated hydroxytoluene (BHT), 1% BHA plus 1% propyl gallate (PG), 1% BHA plus 1% sodium L-ascorbate (SA), 1% BHA plus 1% DL-alpha-tocopherol (alpha-TP), 0.4% BHT plus 0.4% BHA plus 0.4% PG plus 0.4% SA plus 0.4% alpha-TP, 1% BHA or 2% BHA. Further groups of 10 rats each received antioxidants without BHA as controls. Histological examination revealed significantly increased incidences of hyperplasia in the groups given BHA together with SA or PG at the prefundic region or at the mid region respectively. The forestomach changes induced by BHA together with SA were equal to those induced by 2% BHA. On the other hand, simultaneous treatment with BHA and PG or alpha-TP reduced the incidence of hyperplasia at the prefundic region. It is concluded that mixed treatment with BHA and other antioxidants exerted enhancing or inhibitory effects on the induction of hyperplasia at different sites of the forestomach epithelium.