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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
Authors:J Ross  G Nelson  G Erexson  A Kligerman  K Earley  R C Gupta  S Nesnow
Affiliation:Carcinogenesis and Metabolism Branch, US Environmental Protection Agency, Research Triangle Park, NC 27711.
Abstract: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-7,8-dione. Among the monohydroxy derivatives, only 2-, 9- and 12-hydroxy-B[a]P produced detectable adducts. The only disubstituted derivative studied that produced adducts was the trans-7,8-dihydrodiol. 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-trans-7,8-dihydrodiol 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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