Carcinogen-DNA Adduct Formation in the Lungs and Livers of Preweanling CD-I Male Mice following Administration of [3H]-6-Nitrochrysene, [3H]-6-Aminochrysene, and [3H]-l,6-Dinitropyrene

6-Nitrochrysene (NC) and 6-aminochrysene (AC) have been shown to be potent lung and liver carcinogens when administered in multiple i.p. doses to preweanling mice. 1,6-Dinitropyrene has been shown to be a strong hepatocarcinogen but a weak lung carcinogen in this same bioassay. We have examined carcinogen-DNA adduct profiles in the target tissues of preweanling male CD-I mice following administration of single or multiple doses of these compounds. Depending on the tissue and the dosing schedule, the total level of DNA modification in animals dosed with | 'I I|N( was 2to 9-fold higher than in animals dosed with |'I I|A( . Regardless of the dosing schedule, DNA isolated from the lungs and livers of both |3H|NCand [3H|AC-treated preweanling male mice con tained a single major and chromatographically identical adduct. This major adduct, which accounted for as much as 90% of the total carcino gen-DNA adduces in enzymatic hydrolysates from treated animals, was chromatographically distinct from the major C8-purine-substituted adducts formed from the reaction of N-hydroxy-AC with calf thymus DNA. In contrast to the results obtained with NC and AC, the major carcinogenDNA adduct formed in the livers of mice treated with [3H|-l,6-dinitropyrene was found to cochromatograph with l-AKdeoxyguanosin-8yl)animo-6-mtrr.pyrene, a product derived from /V-hydro\y-l-amino-6nitropyrene. Since NC and its nitro-reduced derivative, AC, yielded an identical carcinogen-DNA adduct in vivo and this adduct was not derived from V hydroxy-AC, we conclude that the metabolic activation of NC in the neonatal mouse must involve some previously undescribed combination of ring-oxidation and nitro-reduction pathways. This activation pathway could be an important factor in determining the potency of NC and AC as carcinogens in this bioassay system.