title: Carcinogenicity of aromatic hydrocarbons directly applied to rat mammary gland.
abstract: To obtain some initial evidence on the mechanism(s) of activation of PAH in rat mammary gland, we studied the carcinogenicity of a series of PAH directly applied to this tissue. A series of PAH which are or are not expected to be activated by one-electron oxidation because of their low or high ionization potential (IP), respectively, were tested. The compounds were dispersed as fine powders on an exposed mammary gland of female Sprague-Dawley rats. 5-Methylchrysene, dibenz[a,h]anthracene and benz[a]anthracene, which have relatively high IP, were inactive. In contrast, three PAH with relatively low IP, 7,12-dimethylbenz[a]anthracene, benzo[a]pyrene (BP), and 3-methylcholanthrene (MC), were potent carcinogens, 6-MethylBP, with low IP, and 7-methyl-benz[a]anthracene, with borderline IP, elicited only mesenchymal tumors, whereas BP 7,8-dihydrodiol and cyclopenta[cd]pyrene were inactive. A series of MC derivatives substituted at C-1 or C-2 was tested. Substituents at C-1, the position of activation in the one-electron oxidation pathway, generally suppressed carcinogenic activity. Substitution at C-2 did not eliminate carcinogenic activity, with the exception of MC2-one. These results provide initial information suggesting that one-electron oxidation may be a mechanism of activation for PAH in the mammary gland.
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha 68105-1065.
authors.forename: E
authors.initials: E
authors.lastname: Cavalieri
authors.forename: E
authors.initials: E
authors.lastname: Rogan
authors.forename: D
authors.initials: D
authors.lastname: Sinha
mesh_terms: D000818:Animals; D001711:Biotransformation; D004305:Dose-Response Relationship, Drug; D005260:Female; D008321:Mammary Glands, Animal / Q000187:drug effects*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced*; D011083:Polycyclic Compounds / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
chemical_list: D011083:Polycyclic Compounds