Induction of mouse epidermal ornithine decarboxylase activity and skin tumors by 7,12-dimethylben.
Application of a single large dose (3.6 micromol) or smaller weekly repeated doses (0.2 micromol) of 7,12-dimethylbenz[a]anthracene (DMBA) to the skin of CD-1 mice led to a 20 to 50-fold increase in epidermal ornithine decarboxylase (ODC) (EC 4.1.1.17) activity as well as tumor formation. Retinoic acid (0.17-68 nmol), a potent inhibitor of both the induction of ODC activity and tumor formation by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), failed to inhibit both the induction of ODC activity and tumor formation by DMBA. In contrast, 7,8-benzoflavone (367 nmol), which did not inhibit the induction of ODC activity by TPA, effectively inhibited the induction of ODC activity as well as the formation of skin tumors caused by DMBA. These results indicate that (a) the mechanism of the induction of ODC activity and tumor formation by a complete carcinogen appears to be different from that of the tumor promoter TPA, (b) DMBA-induced ODC activity may be an important component of the mechanism of DMBA carcinogenesis, and (c) the protective effect of retinoic acid on skin carcinogenesis is not universal; it inhibits skin tumor formation by some agents and not by others.
Verma
A K
AK
McArdle Laboratory for Cancer Research, University of Wisconsin, Madison 53706, USA.
Conrad
E A
EA
Boutwell
R K
RK
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology*; D002273:Carcinogens / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004817:Epidermis / Q000187:drug effects / Q000201:enzymology*; D005260:Female; D051379:Mice; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D065108:Ornithine Decarboxylase Inhibitors; D012878:Skin Neoplasms / Q000139:chemically induced / Q000201:enzymology* / Q000517:prevention & control; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000633:toxicity; D014212:Tretinoin / Q000494:pharmacology*
D001571:Benzoflavones; D002273:Carcinogens; D004791:Enzyme Inhibitors; D065108:Ornithine Decarboxylase Inhibitors; D014212:Tretinoin; D015127:9,10-Dimethyl-1,2-benzanthracene; C011512:alpha-naphthoflavone; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate