Sensitivity of HRA/Skh hairless mice to initiation/promotion of skin tumors by chemical treatment

HRA/Skh hairless mice were investigated for their sensitivity to initiation and promotion by chemicals because of (a) the known sensitivity of these mice to photocarcinogenesis, (b) their low background papilloma incidence (2/3000 mice under 1 year of age) and (c) ease of treatment and identification of tumors, in the absence of hair. Employing a variety of treatments with 7,12-dimethylbenza]anthracene (DMBA) as initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as promoter, it was found that the strain was susceptible to both initiation and promotion. Papilloma incidence was at least equivalent to that observed with other sensitive mouse strains. Following initiation with 2.56 micrograms DMBA, papilloma development was promoter-concentration-dependent, resulting in 22.5 papillomas/mouse at 20 weeks in animals administered 5 micrograms TPA. In the absence of DMBA initiation, TPA treatment was weakly carcinogenic in HRA/Skh mice. This treatment induced a dose-dependent increase in papillomas, one of which progressed to a keratoacanthoma-like tumor after 65 weeks. These results show that HRA/Skh mice are highly sensitive, not only to UV carcinogenesis, but also to chemical initiation and promotion of skin papillomas.