Effect of trichloropropene oxide on the ability of polyaromatic hydrocarbons and their "K-region" oxides to initiate skin tumors in mice and to bind to DNA in vitro.
The potent epoxide hydrase inhibitor, 1,1,1-trichloro-2,3-propene oxide (TCPO), enhanced the tumor-initiating ability of benzo[alpha]pyrene (BP) and 3-methylcholanthrene (MCA) but had no effect on 9,10-dimethyl-1,2-anthracene (DMBA) initiation in a two-stage system of tumorigenesis in female Charles River CD-1 mice. The tumor-initiating ability of dibenz[alpha,h]-anthracene (DBA) was decreased by prior topical treatment with 10 mumoles of TCPO. The tumor latency period of BP and MCA was decreased by TCPO but had no effect on DMBA or DBA. Topical treatment with 10 mumoles of TCPO did not initiate tumors in a two-stage system in mouse skin nor did it cause any histopathologic changes in the skin. The "K-region" epoxides of BP, DMBA, and MCA were weak tumor initiators when compared to the parent compounds. TCPO only slightly increased or had no effect on the tumor-initiating activity of the above epoxides. Pretreatment with Croton oil 18 hours prior to initiation with BP-4,5-epoxide also slightly enhanced the tumorigenic response in mouse skin. DBA-5,6-epoxide, when tested as a complete carcinogen at high doses (1 mg daily/10 days), was found to be a weak carcinogen but with activity comparable to that of DBA. TCPO only slightly increased the in vitro epidermally mediated covalent binding of the above parent polycyclic hydrocarbons to DNA.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000287:Administration, Topical; D000818:Animals; D001551:Benz(a)Anthracenes / Q000633:toxicity; D001580:Benzopyrenes / Q000633:toxicity; D003436:Croton Oil / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors; D004852:Epoxy Compounds / Q000633:toxicity; D004988:Ethers, Cyclic / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006843:Hydrocarbons, Chlorinated / Q000008:administration & dosage / Q000494:pharmacology; D066298:In Vitro Techniques; D008748:Methylcholanthrene / Q000633:toxicity; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced; D010212:Papilloma / Q000139:chemically induced*; D011083:Polycyclic Compounds / Q000378:metabolism / Q000633:toxicity*; D012878:Skin Neoplasms / Q000139:chemically induced*; D013329:Structure-Activity Relationship
D001551:Benz(a)Anthracenes; D001580:Benzopyrenes; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D006843:Hydrocarbons, Chlorinated; D011083:Polycyclic Compounds; D008748:Methylcholanthrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D003436:Croton Oil; D004247:DNA; D004851:Epoxide Hydrolases