DEVELOPMENT OF METHODS TO MONITOR EXPOSURE TO 1-NITROPYRENE

On the basis of P-32-postlabeling analysis, treatment of rats with 1-n itropyrene (1-NP) resulted in the formation of multiple DNA adducts in the liver, mammary glands, and peripheral lymphocytes. The one adduct resulting from nitroreduction, N-(deoxyguanosin-8-yl)-1-aminopyrene, constitutes only a minor component among the adducts. In the present s tudy, incubation of calf thymus DNA with mutagenic ring-oxidized metab olites of 1-NP in vitro in the presence and absence of xanthine oxidas e also resulted in the formation of multiple adducts. On the basis of their chromatographic behavior, it appears that DNA adducts derived fr om such metabolites may have been formed in vivo; however, this needs to be confirmed. [H-3]1-NP was given to male and female F344 rats and Sprague-Dawley rats by gavage at five dose levels in the range of 0.1 to 1000 mu g/kg bw. This led to stable hemoglobin adducts accounting f or 0.08 +/- 0.05% of the dose (n = 3 rats). The radioactivity associat ed with hemoglobin following administration of [H-3]1-NP was cleared w ith a half-life of about 14 days, which is faster than that of unmodif ied erythrocytes in the rat (t(1/2) = 30 days). Treatment of the hemog lobin with 1% HCl in acetone, to precipitate the globin, released the radioactivity; it was all bound to the heme moiety. The structures of the heme adducts have not been elucidated; yet, because of their stabi lity, they may be useful as dosimeters for human exposure to 1-NP. The results of this study demonstrate the potential of using hemoglobin a dducts of 1-NP as dosimeters of uptake and metabolic activation of nit ropolynuclear aromatic hydrocarbons (NO2-PAH). These indicators are a prerequisite for cancer risk assessment of NO2-PAH.