Promoting activities of butylated hydroxyanisole, butylated hydroxytoluene and sodium L-ascorbate on forestomach and urinary bladder carcinogenesis initiated with methylnitrosourea in F344 male rats.

The promoting effects of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and sodium L-ascorbate on two-stage carcinogenesis initiated with methylnitrosourea (MNU) in F344 male rats were investigated. Animals were given injections of MNU (20 mg/kg ip) twice a week for 4 weeks, and then basal diet containing 2% BHA, 1% BHT or 5% sodium L-ascorbate for the next 32 weeks. Administration of BHA, BHT or sodium L-ascorbate in the diet significantly increased the incidences per group and numbers per rat of papilloma and papillary or nodular hyperplasia of the urinary bladder, and BHA and BHT also increased the number of cancers per rat. Furthermore BHA significantly increased the incidences of cancer and papilloma in the forestomach of rats initiated with MNU, whereas treatment with BHA alone was associated with papilloma but no carcinoma development in the rat forestomach. The incidence of adenoma, but not adenocarcinoma, of the thyroid was significantly increased by treatment with MNU plus BHT. These results show that BHA, BHT and sodium L-ascorbate have promoting activities on urinary bladder carcinogenesis in rats initiated with MNU, and that BHA also has a promoting effect on forestomach carcinogenesis after initiation with MNU.