STIMULATION OF TGF-BETA-1 MESSENGER-RNA 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-mu-g/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 beta-1 (TGF-beta-1) in epidermis. Two RNA species 1.9 and 2.5 kb, detected by a mouse TGF-beta-1 cDNA probe, were coordinately expressed. The concentration of these species appeared to be maximal 6-12 h after application, and returned to control levels after 48 h. A second, less intense maximum was observed 72-96 h 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-mu-g/week a dose rate of 16-mu-g/week was essentially without activity in increasing TGF-beta-1 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-mu-g tumorigenesis by B[a]P involves a strong tumor-promoting component. The latter further appears to be mediated by increased TGF-beta-1 expression.