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© 1991 Oxford University Press

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DNA adducts in rat lung, liver and peripheral blood lymphocytes produced by i.p. administration of benzo[a]pyrene metabolites and derivatives

Jeffrey Ross, Garret Nelson 1, Gregory Erexson 1, Andrew Kligerman, Karen Earley 2, Ramesh C. Gupta 2 and Stephen Nesnow

Carcinogenesis and Metabolism Branch and Mutagenesis and Cellular Toxicology Branch, Health Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park NC 27711, USA
1Environmental Health, Research, and Testing Inc., PO Box 12199, Research Triangle Park, NC 27709, USA
2Department of of Preventive Medicine and Environmental Health, and Graduate Center for Toxicology, University of Kentucky Lexington, KY 40506, USA

DNA adducts produced in vivo in rat lung, liver and peripheral blood lymphocytes following the i.p. administration of several synthetic benzo[a]pyrene (B[a]P) metabolites and ring-substituted derivatives have been analyzed by the nuclease P1 version of the 32P-postlabeling assay. These include 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11- and 12-hydroxy-B[a]P, (±)-B[a]P-trans-4,5-dihydrodiol, (± )- B[a]P-trans-7,8-dihydrodiol, (±)-B[a]P-trans-9,10-dihydrodiol and B[a]P-7,-dion. Among the monohydroxy derivatives, only 2-, 9- and 12-hydroxy-B[a]P produced detectable adducts. The only dlsubstituted derivative studied that produced adducts was the trans-7,8-dlhydrodiol. The resulting DNA adducts were compared to those produced in each tissue by administration of B[a]P 9-Hydroxy-B[a]P and B[a]P trns-7,8-dihydrodlol each lead to the formation of major B[a]P adducts seen in lung and liver respectively. None of the adducts derived from either 2-hydroxy-B[a]P or 12-hydroxy-B[a]P were observed following administration of B[a]P alone.


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