The in vivo interaction of activated benzo(a)pyrene with DNA phosphates

The ultimate carcinogenic metabolite of benzo(a)- pyrene (BP) is believed to be the anti isomer of the 7,8- BPDE I binds primarily to the although several other adducts have also been reported. The binding of the diol epoxide to the diol-9,10-epoxide (BPDE I). guanine base in DNA phosphodiester linkage in DNA is believed to lead to DNA strand scission. In vitrostudies, however, show little or no binding at this site.

In the present study the in vivobinding of the diol epoxides of BP to the phosphates in DNA were measured using BPDE-DNA was isolated the high sensitivity of fluorescence, from the dorsal skins of mice each exposed to a single treatment of BP. The BPDE-phosphate adducts were then chemically or enzymatically hydrolyzed to selectively release the diol epoxide from the phosphate in the from of highly fluorescent tetrols. The tetrols were separated by HPLC and quantitated by fluorescence.

The chemical and enzymatic methods employed were unable to yield any detectable amounts of tetrol release from The proportion of BPDE modifications at the phosphodiester site are, therefore, below the The possibility of other the BPDE-phosphate adducts. lower limits of detection (2 %). BP metabolites binding to the phosphate backbone have not been ruled out.