Peroxidative activation of o-phenylhydroquinone leads to the formation of DNA adducts in HL-60 cells

Abstract
Using 32P-postlabeling we studied DNA adduct formation in HL-60 cells treated with the o-phenylphenol metabolites o-phenylhydroquinone (o-PHQ) and o-phenylbenzoquinone (o-PBQ). Treatment with 25–500 μM o-PHQ for 8 h produced one principal and three minor adducts with a relative distribution of 80, 10, 6 and 4%. The relative adduct levels from these treatments were 0.26–2.31 adducts/107 nucleotides. Treatment with 25–250 μM o-PBQ for 2 h resulted in a similar level of DNA modification and adduct distribution. Reaction of purified calf thymus DNA with o-PBQ produced one DNA adduct, which did not correspond to the major adduct produced in HL-60 cells. These results show that o-PHQ and o-PBQ can form DNA adducts. Peroxidase activation of o-phenylphenol may therefore play a role in the carcinogenic effect of this compound.