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 less than 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.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002083:Butylated Hydroxyanisole; D003043:Cocarcinogenesis; D004224:Diterpenes; D004334:Drug Administration Schedule; D004848:Epithelium / Q000473:pathology; D007681:Kidney Papillary Necrosis / Q000139:chemically induced / Q000473:pathology; D008297:Male; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D000084562:Retinyl Esters; D013274:Stomach Neoplasms / Q000139:chemically induced* / Q000473:pathology; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000633:toxicity
D004224:Diterpenes; D000084562:Retinyl Esters; D014801:Vitamin A; D002083:Butylated Hydroxyanisole; C009166:retinol acetate