Tissue distribution of DNA adducts in pre-weanling BLU:Ha mice treated with a tumorigenic dose of fluoranthene.
Fluoranthene (FA), a ubiquitous atmospheric pollutant, is tumorigenic to the lung when injected into BLU:Ha mice 1, 8, and 15 days after birth. DNA adducts were measured by a modified HPLC-32P-postlabeling method in target (lung) and non-target (liver, kidney, spleen plus thymus) organs of 16-day-old mice 24 h after the last treatment with a tumorigenic dose (3.5 mg/mouse) of FA. The anti-FADE adduct was the major DNA adduct and was present at levels ranging from 3.5 to 37 adducts per 10(8) nucleotides (106-1138 fmols/mg DNA) in all DNA samples from the organs of FA-treated mice. The lung contained anti-FADE adduct levels approximately 2, 2.5 and 5 times higher than those in kidney, liver, and spleen plus thymus, respectively. There was no significant difference between anti-FADE adduct levels in liver and kidney; however, adduct levels were significantly higher than those in spleen plus thymus. Significant variation was found among litters in anti-FADE adduct levels from lung, liver, and kidney, but not from spleen plus thymus. An unidentified peak was present in the adduct profile of the kidneys of treated but not control animals. Three additional unidentified radioactive peaks were present in adduct profiles of DNA from tissues of both treated and control animals, but their levels were significantly higher in the tissues of treated animals than in controls. Possible correlations between tumorigenic response and DNA adduct formation are discussed.
Wang
J S
JS
Department of Environmental Health Science, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
Busby
W F
WF
Wogan
G N
GN
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics*; D018736:DNA Adducts / Q000032:analysis*; D005260:Female; D005449:Fluorenes / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013154:Spleen / Q000187:drug effects / Q000473:pathology
D018736:DNA Adducts; D005449:Fluorenes; C007738:fluoranthene