MODIFICATION OF BHA FORESTOMACH CARCINOGENESIS IN RATS - INHIBITION BY DIETHYLMALEATE OR INDOMETHACIN AND ENHANCEMENT BY A RETINOID

The long-term effects of butylated hydroxyanisole (BHA), in combinatio n with various other chemicals on the development of forestomach lesio ns in rats were investigated. BHA is a synthetic antioxidant, and the other agents included the glutathione-depleting agent diethylmaleate ( DEM), the anti-inflammatory drugs indomethacin (IM), dexamethazone (DE X), 6-aminocaproic acetate (6-ACA) and FOY (gabexate mesilate), and th e vitamin all-trans-retinol acetate (RA). Concurrent treatment with BH A (1% in diet) and DEM, IM, DEX or FOY for 52 weeks inhibited developm ent of forestomach epithelial hyperplasia as compared to BHA alone, wh ile simultaneous treatment with RA enhanced hyperplastic development. However, the inhibition by DEX or FOY was only partial and in the DEX case, in particular, might have been due to weight loss. Since the mos t effective inhibitory influence on BHA-induced forestomach lesions ex erted in this 1-year experiment was by DEM, a further 2-year experimen t was conducted to confirm whether DEM actually can exert inhibitory e ffects on BHA (2% in diet)-induced forestomach carcinogenesis. The res ults demonstrated that induction of forestomach hyperplasias and papil lomas by BHA was significantly reduced by combination treatment with D EM. Both multiplicity and incidence of forestomach papillomas were sig nificantly decreased, while squamous cell carcinoma development showed a tendency for decrease only.