Stimulation of TGF-β1 mRNA concentration in mouse skin treated with benzo[a]pyrene

Topical application of benzo[a]pyrene (B[a]P) at dose rates of 32 or 64 μg/week to the dorsal skin of female Swiss (ICR) mice resulted in a marked and rapid increase in concentration of RNA for transforming growth factor β1 (TGF-β1) in epidermis. Two RNA species 1.9 and 2.5kb, detected by a mouse TGF-β1 cDNA probe, were coordinately expressed. The concentration of these species appeared to be maximal 6–12h after application, and returned to control levels after 48h. A second, less intense maximum was observed 72–96h after treatment. Similar effects were observed in CD-1 and HRS (both hr/hr and hr/+) mice, which are also sensitive to B[a]P tumorigenesis. In comparison with 32 and 64 μg/week a dose rate of 16μg/week was essentially without activity in increasing TGF-β1 RNA concentration. All three dose rates induced an increase in epidermal RNA for ornithine decarboxylase, however, and with kinetics similar to those observed with the potent tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate. The results obtained support other findings made in this laboratory, that at high dose rates above 16 μg tumorigenesis by B[a]P involves a strong tumor-promoting component. The latter further appears to be mediated by increased TGF-β1 expression.