Co‐carcinogenic Effect of Retinyl Acetate on Forestomach Carcinogenesis of Male F344 Rats Induced with Butylated Hydroxyanisole

The potential modifying effect of retinyl acetate (RA) on butylated hydroxyanisole (BHA)‐induced rat forestomach tumorigenesis was examined. Male F344 rats, 5 weeks of age, were maintained on diet containing 1% or 2% BHA by weight and simultaneously on drinking water supplemented with RA at various concentrations (w/v) for 52 weeks. In groups given 2% BHA, although marked hyperplastic changes of the forestomach epithelium were observed in all animals, co‐administration of 0.25% RA significantly (P<0.05) increased the incidence of forestomach tumors (squamous cell papilloma and carcinoma) to 60% (9/15, 2 rats with carcinoma) from 15% (3/20, one rat with carcinoma) in the group given RA‐free water. In rats given 1% BHA, RA co‐administered at a dose of 0.05, 0.1, 0.2 or 0.25% showed a dose‐dependent enhancing effect on the development of the BHA‐induced epithelial hyperplasia. Tumors, all papillomas, were induced in 3 rats (17%) with 0.25% RA and in one rat (10%) with 0.05% RA co‐administration. RA alone did not induce hyperplastic changes in the forestomach. These findings indicate that RA acted as a co‐carcinogen in the BHA forestomach carcinogenesis of the rat.