Peroxidase activation of hydroquinone results in the formation of DNA adducts in HL-60 cells, mouse bone marrow macrophages and human bone marrow.
Metabolism of benzene results in the formation of multiple metabolites, including hydroquinone (HQ). HQ is a reducing co-substrate for peroxidase enzymes, and the resultant semiquinone and para-benzoquinone (p-BQ) may bind to DNA. The role of peroxidase activation in the formation of DNA adducts by benzene metabolites has not been established. In this study we investigated the role of peroxidase activation in the formation of DNA adducts by HQ and p-BQ in HL-60 cells, human bone marrow (HBM) cells, mouse bone marrow macrophages (MBMM) and the U-937 and Raji leukemia cell lines. Adduct formation was measured by P1-enhanced 32P-postlabeling; peroxidase activity was measured with a spectrophotometric assay. Treatment with p-BQ resulted in the formation of two DNA adducts in all of the cell lines. The DNA adducts were identical in all of the cells, however, the adduct level varied by 80-fold. Treatment with HQ produced one DNA adduct in HL-60 cells, HBM and MBMM; no adducts were detected in U-937 or Raji cells. The HQ-DNA adducts in the three cell lines were identical. The adduct level was highest in the HL-60 cells, followed by HBM and MBMM. There was a statistically significant correlation between peroxidase activity and the formation of HQ-DNA adducts. These results suggest that peroxidase-mediated metabolism is involved in the activation of HQ to form DNA adducts in mouse bone marrow and HBM.
Lévay
G
G
Department of Neurological Surgery, School of Medicine, University of California, San Francisco 94143.
Ross
D
D
Bodell
W J
WJ
D000818:Animals; D016227:Benzoquinones / Q000378:metabolism; D001711:Biotransformation; D001853:Bone Marrow / Q000378:metabolism*; D002460:Cell Line; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D006873:Hydroquinones / Q000378:metabolism*; D007938:Leukemia; D015473:Leukemia, Promyelocytic, Acute; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010544:Peroxidases / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D016227:Benzoquinones; D004273:DNA, Neoplasm; D006873:Hydroquinones; C004532:quinone; D004247:DNA; D010544:Peroxidases; C031927:hydroquinone