2-Aminofluorene metabolism and DNA adduct formation by mononuclear leukocytes from rapid and slow acetylator mouse strains.
Levy-GN; Chung-G; Weber-WW
Carcinogenesis 1994 Feb; 15(2):353-357
The ability of several types of immune cells from C57BL/6J-mice (B6) and A/J-mice and their acetylator congenic strains (B6.A-NatS and A.B6-NatR, respectively) to metabolize aminofluorene (153786) (AF) and form DNA-AF adducts was examined. Mononuclear leukocytes (MNL) metabolized AF to its acetylated form 2-acetylaminofluorene (53963) (AAF). MNL from the rapid acetylator strain, B6, produced twice as much AAF as the MNL from the slow acetylator strain, B6.A-NatS. Increasing concentrations of AF in the culture media resulted in the increased production of AAF except at 100 micromolar AF. Likewise, increasing the amount of time the cells were exposed to AF increased the production of AAF. Para-aminobenzoic-acid (150130) (PABA) was more readily acetylated than AF and the differences in the amount of acetylated PABA between rapid and slow acetylator strains were significant. Both lymphocytes and monocytes acetylated AF but lymphocytes had a greater acetylating activity per one million cells than monocytes. High performance liquid chromatography analysis of AF metabolites of MNL from B6 and B6.A-NatS-mice only showed peaks corresponding to AF and AAF. Metabolites from A/J and A.B6-NatR- mice showed additional peaks which may be oxidation products. DNA adduct formation was two to three times higher in the rapid acetylator strains of mice, 0.8 to 3.5 picomoles of adduct per milligram of DNA, than in the slow acetylator strains, 0.79 picomoles of adduct per microgram of DNA.
NIOSH-Publication; NIOSH-Grant; Cancer; In-vitro-study; Blood-cells; Biological-effects; Carcinogens; Fluorenes; Amino-compounds; DNA-damage; Genotoxic-effects; Dose-response; Metabolic-study
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University of Michigan at Ann Arbor, Ann Arbor, Michigan