title: 9-Sulfooxymethylanthracene is an ultimate electrophilic and carcinogenic form of 9-hydroxymethylanthracene.
abstract: The role of electrophilic hydroxymethyl sulfate esters in the metabolic activation, DNA-damage, mutagenicity, and complete carcinogenicity of polycyclic aromatic hydrocarbons has been elucidated considerably in recent years. The observations are in agreement with a unified hypothesis which predicts that electrophilic hydroxymethyl sulfate esters and closely related aralkylating agents are major ultimate carcinogenic forms of most, if not all, carcinogenic alkyl-substituted and even unsubstituted carcinogenic polycyclic aromatic hydrocarbons. The common final step in a chain of enzymatic substitution reactions is the formation of an aralkylating agent bearing a good leaving group. Activation of hydroxymethyl derivatives, including 9-hydroxymethylanthracene, to electrophilic mutagens has been shown to be catalyzed by 3'-phosphoadenosine-5'-phosphosulfate-dependent sulfotransferase activity. Recent studies, in a complete carcinogenic model, demonstrate that a number of sulfuric acid ester derivatives are more potent than their hydroxymethyl precursors by repeated subcutaneous injection in female Sprague-Dawley rats. In this paper, these observations have been extended to include 9-sulfooxymethylanthracene as an ultimate electrophilic and carcinogenic form of 9-hydroxymethylanthracene.
authors.affiliation: Department of Pharmacology, Experimental Cancer Research Laboratory, and Graduate Center for Toxicology, Albert B. Chandler Medical Center, University of Kentucky, Lexington, Kentucky, 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; D000873:Anthracenes / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism*; D002273:Carcinogens / Q000008:administration & dosage / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007279:Injections, Subcutaneous; D009374:Neoplasms, Experimental / Q000139:chemically induced; D011084:Polycyclic Aromatic Hydrocarbons / Q000008:administration & dosage / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015238:Sulfotransferases / Q000008:administration & dosage / Q000378:metabolism; D013463:Sulfuric Acid Esters / Q000378:metabolism
chemical_list: C115414:9-sulfooxymethylanthracene; D000873:Anthracenes; D002273:Carcinogens; D011084:Polycyclic Aromatic Hydrocarbons; D013463:Sulfuric Acid Esters; C049587:9-hydroxymethylanthracene; D015238:Sulfotransferases; C084556:ethinylestradiol-17 alpha sulfotransferase