COMPARISON OF DNA ADDUCT FORMATION IN MICE FED COAL-TAR OR BENZO[A]PYRENE

Coal tar is a complex mixture containing hundreds of compounds, including the carcinogenic polycyclic aromatic hydrocarbon, benzo[a]pyrene. In order to compare the metabolic activation of a single carcinogen versus a complex mixture containing the carcinogen, we determined the DNA adduct profiles in B6C3F(1) mice fed doses of coal tar or benzo[a]pyrene at concentrations corresponding to the amount of benzo[a]pyrene found in the respective coal tar treatments. DNA adduct formation was quantified in liver, lungs and forestomach by P-32-postlabeling and was found to increase as a function of dose in each tissue with both coal tar and benzo[a]pyrene. In mice fed benzo[a]pyrene, a major adduct was detected with the same elution characteristics by TLC and HPLC as the major adduct, 10 beta-(deoxyguanosin-N-2-yl)-7 beta,8 alpha,9 alpha-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (dG-N-2-BPDE), obtained from reacting (+/-)-antibenzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) with DNA. DNA binding was in the order forestomach greater than or equal to liver > lung, except at the highest dose group where the order was liver > forestomach > lung. In mice fed coal tar, a diagonal zone of radioactivity with a number of discrete adducts was observed. One area of radioactivity contained the major BPDE adduct, dG-N-2-BPDE, based on co-elution by TLC and HPLC with the synthesized adduct. Total DNA binding was greater in the coal tar-fed mice than in the mice fed benzo[a]pyrene, and the adduct levels were in the order lung > liver > forestomach. These results indicate that there are tissue-specific differences in the activation of coal tar components when compared to a representative carcinogen contained within the mixture.