FORMATION AND PERSISTENCE OF DNA-ADDUCTS IN ORGANS OF CD-1 MICE TREATED WITH A TUMORIGENIC DOSE OF FLUORANTHENE

Fluoranthene (FA) is tumorigenic to the lung when injected i.p. into C D-1 mice 1, 8 and 15 days after birth (Wang, J.-S. and Busby, W.F.Jr, Carcinogenesis, 14, 1871-1874, 1993). Levels, tissue distribution and persistence of FA-DNA adducts detected by HPLC-P-32-postlabeling were investigated during the course of lung tumorigenesis by FA. -1,2,3-tri hydroxy-1,2,3,10b-tetrahydrofluoranthene (anti-FADE adduct) was consis tently the major adduct in DNA samples from lung, heart, liver and kid ney of animals examined at different time points from 2 h to 165 days after the last treatment with the tumorigenic dose (3.5 mg/mouse) of F A, Several unidentified adducts were also detected, Lung, the target o rgan for FA tumorigenicity, contained higher levels of anti-FADE adduc t than other tissues from 1-165 days after treatment, The anti-FADE ad duct level decreased in a biphasic manner after reaching maximum value s at 2 h in heart and spleen plus thymus and 3 days in lungs, liver an d kidneys. About 10% of the maximum amount of anti-FADE adduct remaine d in lung, liver and heart 165 days after final FA treatment, at which time 44% of animals had developed lung adenomas. Significant inter-li tter variations, but no sex differences in adduct levels were observed , These results indicated a positive correlation between anti-FADE add uct level and persistence in relation to target organ specificity for tumor formation.