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

Coal tar is a complex mixture containing hundreds of compounds, includ ing the carcinogenic polycyclic aromatic hydrocarbon, benzo[a]pyrene. In order to compare the metabolic activation of a single carcinogen ve rsus a complex mixture containing the carcinogen, we determined the DN A adduct profiles in B6C3F(1) mice fed doses of coal tar or benzo[a]py rene at concentrations corresponding to the amount of benzo[a]pyrene f ound in the respective coal tar treatments. DNA adduct formation was q uantified 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 wa s detected with the same elution characteristics by TLC and HPLC as th e 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 f rom reacting -)-antibenzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) with DNA. DNA binding was in the order forestomach greater than or eq ual 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 a rea of radioactivity contained the major BPDE adduct, dG-N-2-BPDE, bas ed on co-elution by TLC and HPLC with the synthesized adduct. Total DN A binding was greater in the coal tar-fed mice than in the mice fed be nzo[a]pyrene, and the adduct levels were in the order lung > liver > f orestomach. These results indicate that there are tissue-specific diff erences in the activation of coal tar components when compared to a re presentative carcinogen contained within the mixture.