Role of hydrogen peroxide in the formation of DNA adducts in HL-60 cells treated with benzene metabolites.
We have investigated the influence of peroxides on DNA adduct formation in HL-60 cells treated with polyphenolic metabolites of benzene. Treatment of HL-60 cells with 50 microM hydroquinone (HQ), 500 microM catechol (CAT) or 200 microM 1,2,4-benzenetriol (BT) resulted in adduct levels of 0.27, 0.21 and 0.21 x 10(-7), respectively. Addition of 50-250 microM H2O2 or 250 microM cumene hydroperoxide to HL-60 cells increased DNA adduct formation 2.7-10-fold following treatment with HQ or CAT but had no effect on adduct formation by BT. Treatment of HL-60 cells with the combinations of HQ plus either BT or phorbol myristate acetate (PMA) potentiated DNA adduct formation by 2.5-4-fold. Significant elevations of cellular H2O2 levels occurred after treatment of HL-60 cells with either PMA, CAT or BT. These results indicate that cellular levels of H2O2 regulate the peroxidase dependent activation of benzene metabolites to form DNA adducts.
Lévay
G
G
Brain Tumor Research Center of the Department of Neurological Surgery, School of Medicine, University of California, San Francisco 94143-0806, USA.
Bodell
W J
WJ
D001555:Benzene Derivatives / Q000737:chemistry; D002396:Catechols / Q000737:chemistry*; D018736:DNA Adducts / Q000737:chemistry*; D018922:HL-60 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry*; D006873:Hydroquinones / Q000737:chemistry*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001555:Benzene Derivatives; D002396:Catechols; D018736:DNA Adducts; D006873:Hydroquinones; C013038:hydroxyhydroquinone; D006861:Hydrogen Peroxide; C034221:catechol; D013755:Tetradecanoylphorbol Acetate; C007164:cumene hydroperoxide; C031927:hydroquinone