Formation and persistence of DNA adducts in organs of CD-1 mice treated with a tumorigenic dose of fluoranthene

Carcinogenesis. 1995 Nov;16(11):2609-16. doi: 10.1093/carcin/16.11.2609.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carcinogens / metabolism*
  • DNA Adducts / metabolism*
  • Female
  • Fluorenes / metabolism*
  • Male
  • Mice
  • Organ Specificity
  • Pregnancy
  • Sex Factors
  • Tissue Distribution

Substances

  • Carcinogens
  • DNA Adducts
  • Fluorenes
  • fluoranthene