P-32 POSTLABELING ANALYSIS OF DIBENZ[A,J]ACRIDINE DNA-ADDUCTS IN MICE- PRELIMINARY DETERMINATION OF INITIAL GENOTOXIC METABOLITES AND THEIR EFFECT ON BIOMARKER LEVELS

N-Heterocyclic aromatics (NHA) are widely occurring environmental poll utants formed during the pyrolysis of nitrogen-containing organic chem icals. NHA are found in significant amounts in tobacco condensates, sy nthetic fuels, gasoline engine exhaust, and effluents from the heating of coal. Dibenz[a,j]acridine (DBA) is an example of NHA. The potency of many carcinogenic compounds is related, at least in part, to the ef ficiency of their biological activation. We undertook studies to deter mine which initial metabolites of DBA lead to the formation of high le vels of carcinogen-DNA adducts in vivo. DBA and its metabolites, trans -DBA-1,2-dihydrodiol (DBA-1,2-DHD), trans-DBA-3,4-dihydrodiol (DBA-3,4 -DHD), and trans-DBA-5,6-dihydrodiol (DBA-5,6-DHD), were applied to th e skin of mice. DNA was isolated using enzyme-solvent extraction metho d. DNA was P-32-postlabeled under conditions of limiting [P-32]ATP. In skin, DBA produced two distinct adducts. The same two adducts were se en when DBA-3,4-DHD was applied. In addition the total adduct level el icited by DBA-3,4-DHD was higher than that of parent compound. Two add ucts were seen when DBA-5,6DHD was applied, but these were very differ ent from adducts seen with DBA. These results suggested that activatio n of DBA to DNA-binding compounds in skin includes initial formation o f DBA-3,4-DHD. The data support development of biomarkers for the expo sure and effect of this compound, and also suggest that specific metab olic susceptibility markers might be able to predict populations at in creased risk.