Inhibition of the tumor-initiating ability of the potent carcinogen 7,12-dimethylbenz(a)anthracene by the weak tumor initiator 1,2,3,4-dibenzanthracene.
ARyl hydrocarbon hydroxylase (AHH) in mouse epidermis was inducible by topical application of several tumor-initiating polycylic aromatic hydrocarbons. The weak tumor initiator 1,2,3,4-dibenazanthracene (1,2,3,4-DBA), at dose level of 200 nmoles, increased AHH activity more than 10-fold over that of the acetone controls at 12 hr after treatment. Administration of the same quantity of the potent initiator 7,12-dimethylbenz(a)anthracene (DMBA) increased AHH activity approximately 4-fold over that of the control at 12 hr after treatment. Simultaneous treatment with 200 or 100 nmoles of DMBA and 1,2,3,4-DBA resulted in AHH activity that was 546 and 732% that of the controls, respectively, 12 hr after treatment: this was less AHH activity than was observed when 1,2,3,4-DBA was administered alone. Doses of 20 nmoles or more of 1,2,3,4-DBA, when given at about the same time as DMBA, effectively inhibited DMBA initiation of skin tumors in a two stage system of tumorigenesis. The results suggest that the weak initiator 1,2,3,4-DBA may program the epidermal AHH system to metabolize the strong carcinogen DMBA to noncarcinogenic intermediate(s).
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D001551:Benz(a)Anthracenes / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity*; D001667:Binding, Competitive; D002277:Carcinoma / Q000139:chemically induced; D004247:DNA / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced; D010212:Papilloma / Q000139:chemically induced; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced*
D001551:Benz(a)Anthracenes; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA; D001189:Aryl Hydrocarbon Hydroxylases