Carcinogenicity of aromatic hydrocarbons directly applied to rat mammary gland

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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-methylbenz[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, w9th the exception of MC-2-one. These results provide initial information suggesting that one-electron oxidation may be a mechanism of activation for PAH in the mammary gland.