DNA damage induced by metabolites of o-phenylphenol in the presence of copper(II) ion.
Reactivities of o-phenylphenol and its metabolites (2,5-dihydroxybiphenyl, 2-phenyl-1,4-benzoquinone) with DNA were investigated by a DNA sequencing technique, and the reaction mechanism was studied by UV-visible and ESR spectroscopies. In the presence of Cu(II), 2,5-dihydroxybiphenyl caused strong DNA damage even without piperidine treatment. Catalase, methionine, and methional inhibited the DNA damage completely, whereas mannitol, sodium formate, ethanol, tert-butyl alcohol, and superoxide dismutase did not. 2,5-Dihydroxybiphenyl plus Cu(II) frequently induced a piperidine-labile site at thymine and guanine residues. The addition of Fe(III), Mn(II), Co(II), Ni(II), Zn(II), Cd(II), or Pb(II) did not induce DNA damage with 2,5-dihydroxybiphenyl. When H2O2 was added, 2-phenyl-1,4-benzoquinone also induced DNA damage in the presence of Cu(II). Cu(II) accelerated the autoxidation of 2,5-dihydroxybiphenyl to quinone. An ESR study revealed that the semiquinone radical is an intermediate of the autoxidation. Catalase had no inhibitory effect on the acceleration by Cu(II). Superoxide dismutase promoted both the autoxidation of 2,5-dihydroxybiphenyl and the initial rate of semiquinone radical production. ESR spin trapping experiments showed that the addition of Fe(III) produced hydroxyl radical during the autoxidation of 2,5-dihydroxybiphenyl, whereas the addition of Cu(II) hardly did so. The results suggest that DNA damage by 2,5-dihydroxybiphenyl plus Cu(II) is due to active species other than hydroxyl free radical.
Inoue
S
S
Department of Public Health, Faculty of Medicine, Kyoto University, Japan.
Yamamoto
K
K
Kawanishi
S
S
D016227:Benzoquinones / Q000633:toxicity; D001713:Biphenyl Compounds / Q000378:metabolism / Q000633:toxicity*; D003300:Copper / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects*; D005609:Free Radicals; D011905:Genes, ras / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D010084:Oxidation-Reduction; D010761:Phosphorus Radioisotopes; D013056:Spectrophotometry, Ultraviolet
D016227:Benzoquinones; D001713:Biphenyl Compounds; D005609:Free Radicals; D010761:Phosphorus Radioisotopes; C029322:phenylbenzoquinone; D003300:Copper; D006861:Hydrogen Peroxide; C004369:2-phenylphenol