DNA-carcinogen adducts in circulating leukocytes as indicators of arylamine carcinogen exposure.
DNA-carcinogen adducts in leukocytes and putative target tissues (liver and urinary bladder) of C57BL/6J mice were measured by 32P-postlabeling and HPLC analysis after controlled exposure to the arylamine carcinogen 2-aminofluorene (2-AF). After an acute exposure via ip injection, adducts were detected at 3 hr in leukocytes, liver, and bladder. The disappearance of DNA-carcinogen adducts in liver and leukocytes were parallel over the 24-hr period studied. Following a 7-day continuous exposure to 2-AF via drinking water, adduct levels in leukocytes and target tissues were responsive to dose at 30, 100, and 300 ppm. Adduct levels at the highest dose reached 17,000 fmol/mg DNA in leukocytes, 1900 fmol/mg in liver, and 2300 fmol/mg in bladder. Although adduct levels after 7 days were highest in leukocytes, adducts were not detectable in leukocytes 7 days after discontinuing exposure. In contrast, liver and bladder retained approximately 50 and 75% of their respective adduct levels 7 days after exposure was stopped. The results indicate that circulating leukocytes may be useful as indicators of current exposure to arylamine carcinogens. Circulating leukocytes may also be useful as biological monitors of DNA damage in arylamine target tissues during chronic exposure to these compounds. Some important differences in persistence of DNA-carcinogen adducts between leukocytes and target tissues were observed.
Levy
G N
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Department of Pharmacology, University of Michigan, Ann Arbor 48109-0626.
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004249:DNA Damage; D004784:Environmental Monitoring / Q000379:methods*; D005069:Evaluation Studies as Topic; D005449:Fluorenes / Q000633:toxicity*; D007962:Leukocytes / Q000737:chemistry / Q000187:drug effects*; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D001743:Urinary Bladder / Q000737:chemistry / Q000187:drug effects
D002273:Carcinogens; D005449:Fluorenes; C012177:2-aminofluorene