title: 7-Sulfooxymethyl-12-methylbenz[a]anthracene is an exceptionally reactive electrophilic mutagen and ultimate carcinogen.
abstract: The hypothesis was tested that an ultimate carcinogen of 7-hydroxymethyl-12-methylbenz[a]anthracene (HMBA), a major metabolite of 7,12-dimethylbenz[a]anthracene (DMBA), is a benzylic carbonium ion generated from an exceptionally reactive aralkylating metabolite, such as an electrophilic sulfate ester. In conformity with this hypothesis, sarcomas were rapidly induced in rats following repeated subcutaneous injection of HMBA (67%) or its electrophilic sulfate ester, sodium 7-sulfooxymethyl-12-methylbenz[a]anthracene (SMBA) (100%). It would appear from the results summarized here that the search for a carcinogenic metabolite of DMBA has been successful. In addition, an aralkylating electrophilic mutagen and carcinogen has been prepared from HMBA, which is itself either an ultimate carcinogen or a direct precursor of an ultimate carcinogen, i.e., a benzylic carbonium ion.
authors.affiliation: Department of Pharmacology, 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: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012513:Sarcoma, Experimental / Q000139:chemically induced*
chemical_list: D002273:Carcinogens; D009153:Mutagens; C018970:7-hydroxymethyl-12-methylbenz(a)anthracene; D015127:9,10-Dimethyl-1,2-benzanthracene; C033702:7-(hydroxymethyl)-12-methylbenz(a)anthracene sulfate ester