Targeted Expression of Spermidine/Spermine N1-Acetyltransferase Increases Susceptibility to Chemically Induced Skin Carcinogenesis

The study used transgenic mice with targeted expression of spermidine/spermine N1-acetyltransferase (SSAT) in hair follicle keratinocytes to investigate susceptibility to skin cancer. These K6-SSAT transgenic mice, bred onto a tumor-resistant C57BL/6 background, showed a 10-fold increase in epidermal tumors when exposed to a carcinogenesis protocol involving 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate. The transgenic mice exhibited elevated SSAT activity and protein levels, along with increased putrescine and N1-acetylspermidine, indicating enhanced polyamine catabolism. The study concluded that this activation of polyamine catabolism might play a crucial role in chemically induced skin cancer, as evidenced by the early onset and progression to carcinomas in the transgenic mice.