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 CD-1 mice 1, 8 and 15 days after birth (Wang, J.-S. andBusby, W.F.Jr, Carcinogenesis, 14, 1871–1874, 1993). Levels,tissue distribution and persistence of FA-DNA adducts detectedby HPLC-³²P-postlabeling were investigated during the courseof lung tumorigenesis by FA.Anti-10b-N²-deoxyguanosin-1,2,3-trihydroxy-1,2,3,10b-tetrahydrofluoranthene(anti-FADE adduct) was consistently the major adduct in DNAsamples from lung, heart, liver and kidney of animals examinedat different time points from 2 h to 165 days after the lasttreatment with the tumorigenic dose (3.5 mg/mouse) of FA. Severalunidentified adducts were also detected. Lung, the target organfor FA tumorigenicity, contained higher levels of anti-FADEadduct than other tissues from 1–165 days after treatment.The anti-FADE adduct level decreased in a biphasic manner afterreaching maximum values at 2 h in heart and spleen plus thymusand 3 days in lungs, liver and kidneys. About 10% of the maximumamount of anti-FADE adduct remained in lung, liver and heart165 days after final FA treatment, at which time 44% of animalshad developed lung adenomas. Significant inter-litter variations,but no sex differences in adduct levels were observed. Theseresults indicated a positive correlation between anti-FADE adductlevel and persistence in relation to target organ specificityfor tumor formation.