Target Organ Specificity For N-Heterocyclic Aromatics

Abstract N-Heterocyclic aromatics are environmental carcinogenic pollutants. Of these compounds, 7H-dibenzo[c,g]carbazole (DBC) is a liver and skin carcinogen in the mouse by topical application and a lung carcinogen by IP injection, whereas dibenz[a,j]acridine (DBA) is a skin carcinogen by topical application. Using 32P-postlabeling techniques, it was found that DBC-DNA adduct 6 is the major adduct in the liver, consistent with the metabolism of DBC to the 3-OH-DBC; adducts 2 and 3 are major adducts in the skin and adduct 3 is the major adduct in the lung. On the other hand, DBA adduction is apparent only in the skin and is consistent with the initial metabolism to DBA-3, 4-dihydrodiol. These data indicate that the adduct pattern, as well as the proximate metabolites, are target organ specific; these data will have an impact on the development of biomarkers of the carcinogenic process.