Stimulation of TGF-beta 1 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 micrograms/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[] tumorigenesis. In comparison with 32 and 64 micrograms/week a dose rate of 16 micrograms/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 micrograms tumorigenesis by B[a]P involves a strong tumor-promoting component. The latter further appears to be mediated by increased TGF-beta 1 expression.
Sherman
J H
JH
Department of Environmental Health, University of Cincinnati Medical Center, OH 45267-0056.
Baxter
C S
CS
Albert
R E
RE
D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D051379:Mice; D008812:Mice, Hairless; D008813:Mice, Inbred ICR; D009955:Ornithine Decarboxylase / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics*
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D001564:Benzo(a)pyrene; D009955:Ornithine Decarboxylase