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. and Busby, W.F. Jr, Carcinogenesis, 14, 1871-1874, 1993). Levels, tissue distribution and persistence of FA--DNA adducts detected by HPLC-32P-postlabeling were investigated during the course of lung tumorigenesis by FA. Anti-10b-N2-deoxyguanosin-1,2,3,-trihydroxy-1,2,3 10b-tetrahydrofluoranthene [sequence: see text] (anti-FADE adduct) was consistently the major adduct in DNA samples from lung, heart, liver and kidney 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 FA. Several unidentified adducts were also detected. Lung, the target organ for FA tumorigenicity, contained higher levels of anti-FADE adduct than other tissues from 1-165 days after treatment. The anti-FADE adduct level decreased in a biphasic manner after reaching maximum values at 2 h in heart and spleen plus thymus and 3 days in lungs, liver and kidneys. About 10% of the maximum amount of anti-FADE adduct remained in lung, liver and heart 165 days after final FA treatment, at which time 44% of animals had developed lung adenomas. Significant inter-litter variations, but no sex differences in adduct levels were observed. These results indicated a positive correlation between anti-FADE adduct level and persistence in relation to target organ specificity for tumor formation.
Wang
J S
JS
Division of Toxicology, Whitaker College of Health Sciences, Cambridge, MA USA.
Busby
W F
WF
Wogan
G N
GN
D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D018736:DNA Adducts / Q000378:metabolism*; D005260:Female; D005449:Fluorenes / Q000378:metabolism*; D008297:Male; D051379:Mice; D009928:Organ Specificity; D011247:Pregnancy; D012737:Sex Factors; D014018:Tissue Distribution
D002273:Carcinogens; D018736:DNA Adducts; D005449:Fluorenes; C007738:fluoranthene