DNA Adducts Formed By Peroxidase Activation of Benzene Metabolites

Abstract

Abstract DNA adduct formation was examined in HL-60 cells treated with the benzene metabolites p-benzoquinone (p-BQ), hydroquinone (HQ), catechol (CAT), and 1,2,4-benzenetriol (BT). p-BQ was 13-fold more effective at forming DNA adducts than HQ, which was 7-9-fold more effective than CAT and BT. The DNA adduct formed in human bone marrow (HBM) treated with HQ was the same as that in HL-60 cells. Combination treatment of HL-60 cells with HQ and either CAT or BT increased DNA adduct formation 2.2–6.4-fold. In vitro activation of HQ by myeloperoxidase produced the same DNA adduct in purified DNA as in HL-60 cells and HBM treated with HQ. Reaction of calf thymus DNA with p-BQ produced three adducts. The DNA adduct formed in HL-60 cells treated with p-BQ did not correspond to any of the principal adducts formed in DNA reacted with p-BQ. These results suggest that peroxidase enzymes activate benzene metabolites to form DNA adducts in HBM.