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DNA-carcinogen adducts in circulating leukocytes as indicators of arylamine carcinogen exposure.
Fundam Appl Toxicol 1993 Jul; 21(1):23-30
DNA adduct formation induced by 2-aminofluorene (153786) (2AF) was studied in mice. Male C57B-/6J-mice were injected intraperitoneally with 60mg/kg 2AF. They were killed 3, 6, 12, or 24 hours later. DNA was extracted from leukocytes, liver and bladder and analyzed for adducts by phosphorus-32 post labeling and high performance liquid chromatography. Male C57BL/6J-mice were administered 30, 100, or 300 parts per million (ppm) 2AF in their drinking water. They were killed on day seven or after 7 days recovery and the leukocyte, bladder, and liver DNA was extracted and analyzed for adducts. DNA adducts were detected in the leukocytes, liver, and bladder 3 hours after injection with 60mg/kg 2AF. Adduct concentrations were highest in the bladder followed by the liver and leukocytes. C8-(N(2)-aminofluorenyl)-deoxyguanosine-3',5'- diphosphate (dG-C8-AF) was the major adduct. Small amounts of C8- (N(2)-acetylaminofluorenyl)-deoxyguanosine-3',5'-diphosphate were also detected. The concentrations of leukocyte and liver DNA adducts decreased progressively with time. The concentration of bladder DNA adducts decreased with time up to 12 hours; however, the concentration of bladder DNA adducts at 24 hours was greater than at 6 or 12 hours. Seven day exposure to 2AF caused dose related increases in DNA adduction in all tissues. Maximum adduct concentrations in the leukocytes, liver, and bladder were 17,000, 1,900, and 2,300 femtomoles per milligram DNA, respectively. dG-C8- AF was the only adduct detected. Seven days after the last exposure to 300ppm 2AF, no DNA adduction could be detected in the leukocytes. Liver and bladder DNA still had approximately 50 and 75% of their initial adduct burdens. The author concludes that 2AF induces DNA adduction in leukocytes as well as in the target tissues, the liver and bladder. Leukocyte DNA adduction can be used as a marker for current arylamine exposure.
NIOSH-Publication; NIOSH-Grant; Cancer; Arylamines; DNA-adducts; In-vivo-studies; Laboratory-animals; Blood-cells; Liver-tissue; Bladder-tissue; Dose-response; Carcinogens
Pharmacology University of Michigan 6322 Medical Science I Bldg Ann Arbor, MI 48109-0626
Issue of Publication
Fundamental and Applied Toxicology
University of Michigan at Ann Arbor, Ann Arbor, Michigan
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