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N-Heterocyclic aromatics (NHA) are widely occurring environmental pollutants formed during the pyrolysis of nitrogen-containing organic chemicals. NAH are found in significant amounts in tobacco condensates, synthetic fuels, polluted river sediment, and effluents from the heating of coal. Following topical application 7H-dibenzo [c, g] carbazole (DBC) induces cancer in liver as well as skin, indicating that dermal exposure can lead to systemic effect. DBC and dibenz[a,j] acridine (DBA) are examples of NHA. The potency of many carcinogenic compounds is related, at least in part, to the efficiency of their biological activation. We undertook studies to determine which initial metabolites lead to the formation of high levels of carcinogen-DNA adducts in vivo. DBC and DBA´s, DBA, traps-DBA-1,2-dihydrodiol (DBA-1,2-DHD), trans-DBA-3,4-dihydrodiol (DBA-3,4DHD), and traps-DBA-5,6-dihydrodiol (DBA-5.6-DHD), were applied to the skin of mice. There were six adducts that were related to DBC application. These addusts were seen in the target organ, liver at high levels, but at very low levels in non-target organs, skin, lung and kidney. In skin, DBA produced two distinct adducts. The same two adducts were seen when DBA-3,4-DHD was applied. In addition the total adduct level elicited by DBA-3,4-DHD higher than that of parent compound. Two adducts were seen when DBA-5,6-DHD was applied, but these were very different from adducts seen with DBA. These results suggested that activation of DBA to DNA-binding compounds in skin includes initial formation of DBA-3,4-DHD.
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