Role of Hydrogen Peroxide in the Formation of DNA Adducts in HL-60 Cells Treated with Benzene Metabolites

Abstract

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 μM hydroquinone (HQ), 500 μM catechol (CAT) or 200 μM 1,2,4-benzenetriol (BT) resulted in adduct levels of 0.27, 0.21 and 0.21 × 10−7, respectively. Addition of 50–250 μM H2O2or 250 μM 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 H2O2levels occurred after treatment of HL-60 cells with either PMA, CAT or BT. These results indicate that cellular levels of H2O2regulate the peroxidase dependent activation of benzene metabolites to form DNA adducts.