Effects of retinoids and inhibitors of arachidonic acid metabolism on tumor-promoter-induced soft agar colony formation of mouse epidermal cells and rat urinary bladder cells

Abstract

Effects of retinoids and inhibitors of arachidonic acid metabolism on tumor-promoter-induced soft agar colony formation of mouse epidermal cells and rat bladder cells were evaluated. Topical application of retinoic acid, an anti-tumor-promoter, to female SENCAR mouse skin inhibited 12-O-tetradecanoylphorbol-13-acetate-induced soft agar colony formation of mouse epidermal cells, an event proposed to be essential for tumor promotion. Effects of dietary retinyl acetate, nordihydroguaiaretic acid (NDGA) and quinacrine hydrochloride on colony formation of rat bladder cells were then examined. Male Fischer 344 rats were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine for 3 weeks, followed immediately by the administration for 9 weeks of 5% sodium saccharin supplemented with or without 0.05% retinyl acetate, 0.1% NDGA or 0.01% quinacrine hydrochloride. Saccharin-induced colony growth was significantly inhibited by the administration of retinyl acetate or NDGA, suggesting that these two agents have anti-tumor-promoting effects on rat bladder carcinogenesis. Thus, the colony-forming assay might be useful for early detection of anti-tumor-promoters of skin and bladder.