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DNA damage resulting from the oxidation of hydroquinone by copper: role for a Cu(II)/Cu(I) redox cycle and reactive oxygen generation.
Carcinogenesis. 1993 Jul; 14(7):1303-11.C

Abstract

The myelotoxicity, including leukemia, associated with benzene exposure has been attributed to the further activation of benzene-derived metabolites. In a previous study, we observed that (Cu(II) strongly mediates the oxidation of hydroquinone (HQ) producing benzoquinone (BQ) and H2O2 through Cu(II)/Cu(I) redox mechanism. Since copper exists in the nucleus and is closely associated with chromosomes and DNA, in this study we investigated whether this chemical--metal redox system induces strand breaks in phi X-174 RFI plasmid DNA. In the presence of micromolar concentrations of Cu(II) and HQ, both single and double strand breaks were induced, whereas HQ, Cu(II), H2O2 or BQ alone at the employed concentrations elicited no significant damage to DNA. The HQ/Cu(II) system was at least twice as efficient as a H2O2/Cu(II) system at inducing DNA strand breaks. Of Cu(II), Fe(III), Mn(II), Cd(II) and Zn(II), only HQ/Cu(II) induced extensive DNA strand breaks. Among HQ, 1,2,4-benzenetriol (BT), catechol and phenol, HQ/Cu(II) and BT/Cu(II) were the two most efficient DNA cleaving systems. The presence of bathocuproinedisulfonic acid (BCS) or catalase prevented the HQ/Cu(II)-induced DNA strand breaks. In addition, the HQ/Cu(II)-induced DNA strand breaks could be completely blocked by reduced glutathione and dithiothreitol, but not by L-cysteine. The interaction of L-cysteine with copper in the absence of HQ induced significant DNA strand breaks with the same pattern of DNA strand breaks as that of HQ/Cu(II) plus L-cysteine. In contrast to the HQ/Cu(II) system, a HQ/myeloperoxidase (MPO)/H2O2 system did not induce any DNA strand breaks, and furthermore, the presence of MPO inhibited the HQ/Cu(II)-induced DNA strand breaks. When DNA pretreated with Cu(II) was exposed to HQ, DNA strand breaks were formed that could be prevented by BCS or catalase, indicating that DNA-bound copper can undergo redox cycling in the presence of HQ, generating H2O2. Similar to the H2O2/Cu(II) system, the HQ/Cu(II)-induced DNA strand breaks could not be efficiently inhibited by hydroxyl radical scavengers but could be protected by singlet oxygen scavengers, indicating that the localized generation of singlet oxygen or a singlet oxygen-like entity, possibly a copper-peroxide complex, rather than free hydroxyl radical probably plays a role in the HQ/Cu(II)-induced DNA strand breaks. The above results suggest that macromolecule-associated copper and reactive oxygen generation may be important factors in the mechanism of HQ-induced DNA damage in target cells.

Authors+Show Affiliations

Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, MD 21205.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8392444

Citation

Li, Y, and M A. Trush. "DNA Damage Resulting From the Oxidation of Hydroquinone By Copper: Role for a Cu(II)/Cu(I) Redox Cycle and Reactive Oxygen Generation." Carcinogenesis, vol. 14, no. 7, 1993, pp. 1303-11.
Li Y, Trush MA. DNA damage resulting from the oxidation of hydroquinone by copper: role for a Cu(II)/Cu(I) redox cycle and reactive oxygen generation. Carcinogenesis. 1993;14(7):1303-11.
Li, Y., & Trush, M. A. (1993). DNA damage resulting from the oxidation of hydroquinone by copper: role for a Cu(II)/Cu(I) redox cycle and reactive oxygen generation. Carcinogenesis, 14(7), 1303-11.
Li Y, Trush MA. DNA Damage Resulting From the Oxidation of Hydroquinone By Copper: Role for a Cu(II)/Cu(I) Redox Cycle and Reactive Oxygen Generation. Carcinogenesis. 1993;14(7):1303-11. PubMed PMID: 8392444.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - DNA damage resulting from the oxidation of hydroquinone by copper: role for a Cu(II)/Cu(I) redox cycle and reactive oxygen generation. AU - Li,Y, AU - Trush,M A, PY - 1993/7/1/pubmed PY - 1993/7/1/medline PY - 1993/7/1/entrez SP - 1303 EP - 11 JF - Carcinogenesis JO - Carcinogenesis VL - 14 IS - 7 N2 - The myelotoxicity, including leukemia, associated with benzene exposure has been attributed to the further activation of benzene-derived metabolites. In a previous study, we observed that (Cu(II) strongly mediates the oxidation of hydroquinone (HQ) producing benzoquinone (BQ) and H2O2 through Cu(II)/Cu(I) redox mechanism. Since copper exists in the nucleus and is closely associated with chromosomes and DNA, in this study we investigated whether this chemical--metal redox system induces strand breaks in phi X-174 RFI plasmid DNA. In the presence of micromolar concentrations of Cu(II) and HQ, both single and double strand breaks were induced, whereas HQ, Cu(II), H2O2 or BQ alone at the employed concentrations elicited no significant damage to DNA. The HQ/Cu(II) system was at least twice as efficient as a H2O2/Cu(II) system at inducing DNA strand breaks. Of Cu(II), Fe(III), Mn(II), Cd(II) and Zn(II), only HQ/Cu(II) induced extensive DNA strand breaks. Among HQ, 1,2,4-benzenetriol (BT), catechol and phenol, HQ/Cu(II) and BT/Cu(II) were the two most efficient DNA cleaving systems. The presence of bathocuproinedisulfonic acid (BCS) or catalase prevented the HQ/Cu(II)-induced DNA strand breaks. In addition, the HQ/Cu(II)-induced DNA strand breaks could be completely blocked by reduced glutathione and dithiothreitol, but not by L-cysteine. The interaction of L-cysteine with copper in the absence of HQ induced significant DNA strand breaks with the same pattern of DNA strand breaks as that of HQ/Cu(II) plus L-cysteine. In contrast to the HQ/Cu(II) system, a HQ/myeloperoxidase (MPO)/H2O2 system did not induce any DNA strand breaks, and furthermore, the presence of MPO inhibited the HQ/Cu(II)-induced DNA strand breaks. When DNA pretreated with Cu(II) was exposed to HQ, DNA strand breaks were formed that could be prevented by BCS or catalase, indicating that DNA-bound copper can undergo redox cycling in the presence of HQ, generating H2O2. Similar to the H2O2/Cu(II) system, the HQ/Cu(II)-induced DNA strand breaks could not be efficiently inhibited by hydroxyl radical scavengers but could be protected by singlet oxygen scavengers, indicating that the localized generation of singlet oxygen or a singlet oxygen-like entity, possibly a copper-peroxide complex, rather than free hydroxyl radical probably plays a role in the HQ/Cu(II)-induced DNA strand breaks. The above results suggest that macromolecule-associated copper and reactive oxygen generation may be important factors in the mechanism of HQ-induced DNA damage in target cells. SN - 0143-3334 UR - https://www.unboundmedicine.com/medline/citation/8392444/DNA_damage_resulting_from_the_oxidation_of_hydroquinone_by_copper:_role_for_a_Cu_II_/Cu_I__redox_cycle_and_reactive_oxygen_generation_ L2 - https://academic.oup.com/carcin/article-lookup/doi/10.1093/carcin/14.7.1303 DB - PRIME DP - Unbound Medicine ER -