Peroxidative activation of o-phenylhydroquinone leads to the formation of DNA adducts in HL-60 cells.
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 microM 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/10(7) nucleotides. Treatment with 25-250 microM 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.
Horvath
E
E
Department of Neurological Surgery, University of California, School of Medicine, San Francisco 94143.
Levay
G
G
Pongracz
K
K
Bodell
W J
WJ
D016227:Benzoquinones; D001711:Biotransformation; D001713:Biphenyl Compounds / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006873:Hydroquinones / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D007942:Leukemia, Experimental / Q000378:metabolism*; D007951:Leukemia, Myeloid / Q000378:metabolism*; D010084:Oxidation-Reduction; D014407:Tumor Cells, Cultured
D016227:Benzoquinones; D001713:Biphenyl Compounds; D004273:DNA, Neoplasm; D006873:Hydroquinones; C029322:phenylbenzoquinone; C066330:phenylhydroquinone