title: Bioalkylation of benz[a]anthracene as a biochemical probe for carcinogenic activity. Lack of bioalkylation in a series of six noncarcinogenic polynuclear aromatic hydrocarbons.
abstract: Seven polynuclear aromatic hydrocarbons were individually studied for evidence of bioalkylation at the site of sc injection in male Sprague-Dawley rats. The metabolism of benz[a]anthracene, a weakly carcinogenic hydrocarbon, was compared to the metabolism of six noncarcinogenic hydrocarbons (benzo(e)pyrene, pyrene, phenanthrene, coronene, triphenylene, and perylene). Twenty-four hr after administration, the tissue in contact with the hydrocarbon was visualized under UV light, excised, and processed as described in the text to determine whether the hydrocarbon had undergone a bioalkylation substitution reaction in vivo. Although the bioalkylation substitution reaction was found to occur readily with the weakly carcinogenic hydrocarbon, benz[a]anthracene, no evidence for bioalkylation or other biochemical reactions were obtained for the noncarcinogenic hydrocarbons. These observations are in accord with a unified hypothesis that the first step in the metabolic activation of unsubstituted carcinogenic hydrocarbons is the biochemical introduction of an alkyl group, most favorably in the meso-anthracenic centers of highest chemical or biochemical reactivity in the molecule.
authors.affiliation: Department of Pharmacology, University of Kentucky, Lexington 40536.
authors.forename: J W
authors.initials: JW
authors.lastname: Flesher
authors.forename: S R
authors.initials: SR
authors.lastname: Myers
mesh_terms: D000478:Alkylation; D000818:Animals; D001551:Benz(a)Anthracenes / Q000378:metabolism* / Q000633:toxicity; D002273:Carcinogens / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry; D007279:Injections, Subcutaneous; D008297:Male; D013058:Mass Spectrometry; D011083:Polycyclic Compounds / Q000378:metabolism* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D013056:Spectrophotometry, Ultraviolet
chemical_list: D001551:Benz(a)Anthracenes; D002273:Carcinogens; D011083:Polycyclic Compounds; C030935:benz(a)anthracene