Establishment and Validation of an Ultra-Short-Term Skin Carcinogenicity Bioassay Using Tg-rasH2 Mice.

ABSTRACT

After initiation with 7,12-dimethylbenz[a]anthracene (DMBA), the promoting potential of 12-O-tetradecanoylphorbol-13-acetate (TPA) on skin tumor development can be detected by an ultra-short-term skin carcinogenicity bioassay using Tg-rasH2 mice. In the present study, 10 chemicals were assessed using this ultra-short-term bioassay as a first step to validate this practical and easy-to-use skin carcinogenicity bioassay. These chemicals belonged to 4 categories dermal vehicles (acetone, 99.5% ethanol, anhydrous ethanol, and Vaseline), skin noncarcinogens (oleic acid diethanolamine condensate, benzethonium chloride, and diisopropylcarbodiimide), skin tumor promoters (TPA and benzoyl peroxide), and a skin carcinogen (4-vinyl-1-cyclohexene diepoxide). In a first study, DMBA was used as the initiator at a dose of 50 µg according to previous data, but skin tumors were observed in the no-treatment and vehicle groups. Therefore, the dose of DMBA for skin tumor initiation was reevaluated using 12.5 or 25 µg, with 12.5 µg found to be sufficient for initiation activity. In the ultra-short-term assay, the vehicles and skin noncarcinogens were negative while the skin tumor promoters and the skin carcinogen were positive. The detection of skin tumor promotion and carcinogenicity was feasible in only 8 weeks. In conclusion, this carcinogenicity bioassay may represent a useful tool for the assessment of the carcinogenicity potential of topically applied chemicals.