retinol-acetate and Urinary-Bladder-Neoplasms

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.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Colony-Forming Units Assay; Diterpenes; Epidermis; Female; Male; Masoprocol; Mice; Quinacrine; Rats; Rats, Inbred F344; Retinoids; Retinyl Esters; Saccharin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Tumor Stem Cell Assay; Urinary Bladder Neoplasms; Vitamin A

Virgin female C3H/He mice (275) were fed a ration that included 0.1 per cent N-4-(5-nitro-2-furyl)-2-thiazolyl formamide (FANFT) and retinyl acetate. The mice were divided into five groups with Groups 1 through 4 receiving 300, 600, 1200, and 2400 IU of retinyl acetate per kilogram of feed plus FANFT respectively. Group 5 received 300 IU per kg of feed and no FANFT as a control. After 45 weeks the bladders were removed and inspected for neoplasms. There were no tumors found in any of the mice from Group 5. It was found that retinyl acetate significantly inhibited the formation of squamous cell tumors at all levels and inhibited transitional cell carcinoma when given as 600 IU per kilogram of feed.

Topics: Animal Feed; Animals; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Diet; Diterpenes; FANFT; Female; Mice; Retinyl Esters; Urinary Bladder Neoplasms; Vitamin A