title: 6-sulfooxymethylbenzo[a]pyrene is an ultimate electrophilic and carcinogenic form of the intermediary metabolite 6-hydroxymethylbenzo[a]pyrene.
abstract: Previous experiments have demonstrated that the intermediary metabolite 6-hydroxymethylbenzo[a] pyrene (HMBP) can be activated to the electrophilic mutagen, 6-sulfooxymethylbenzo[a]pyrene (SMBP), by rat and mouse liver PAPS-dependent sulfotransferase activity or by chemical synthesis. This aralkylating metabolite and 6-hydroxymethylbenzo[a]pyrene were individually administered to groups of 12 female Sprague-Dawley rats, at a 0.2 micromol dose three times weekly for 20 doses. SMBP induced sarcomas at the site of injection in 12 of 12 rats by 33 weeks, whereas HMBP induced sarcomas at the site of injection in 12 of 12 rats by 31 weeks. These results, taken together with the results of previous studies, strongly support the hypothesis that the electrophilic mutagen SMBP accounts for most, if not all, of the complete carcinogenicity of the intermediary metabolite HMBP and probably at least some of the complete carcinogenicity of 6-methylbenzo[a]pyrene (MBP), 6-formylbenzo[a]pyrene (formylBP), and even benzo[a]pyrene (BP), all of which are metabolized to HMBP.
authors.affiliation: Department of Pharmacology, and Graduate Center for Toxicology, Albert B. Chandler Medical Center, University of Kentucky, Lexington 40536, USA. JWFLESH@pop.uky.edu
authors.forename: J W
authors.initials: JW
authors.lastname: Flesher
authors.forename: J
authors.initials: J
authors.lastname: Horn
authors.forename: A F
authors.initials: AF
authors.lastname: Lehner
mesh_terms: D000818:Animals; D001580:Benzopyrenes / Q000737:chemistry* / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity*; D005260:Female; D008099:Liver / Q000187:drug effects; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D012513:Sarcoma, Experimental / Q000139:chemically induced
chemical_list: D001580:Benzopyrenes; D002273:Carcinogens; C066039:6-sulfooxymethylbenzo(a)pyrene