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Reactive oxygen species generated from the reaction of copper(II) complexes with biological reductants cause DNA strand scission.
Arch Biochem Biophys. 1998 Sep 15; 357(2):231-9.AB

Abstract

The generation of hydroxyl radicals (.OH) from the reaction of Cu(II) complexes with biological reductants such as ascorbic acid, glutathione, acetylcysteine, and hydroquinone was confirmed by spin-trapping experiments using electron spin resonance (ESR). The following Cu(II) complexes were used: Cu(II)-(CyHH)2 (CyHH, cyclo(L-histidyl-L-histidyl)), Cu(II)(OP)2 (OP, o-phenanthroline), Cu(II)(HGG) (HGG, L-histidyl-glycylglycine), and Cu(II)(en)2 (en, ethylenediamine). The methyl radical adduct of alpha-(pyridyl-4-N-oxide)-N-tert-butylnitrone (POBN-CH3) was obtained from the reaction of ascorbic acid with all Cu(II) complexes used here in the presence of a spin trap, POBN, and dimethyl sulfoxide, indicating the generation of .OH. Glutathione, N-acetylcysteine, and hydroquinone reacted with both Cu(II)(CyHH)2 and Cu(II)(OP)2 to generate POBN-CH3, while these reductants did not react with either Cu(II)(HGG) or Cu(II)(en)2. Interestingly, the formation of POBN-CH3 in the reaction of Cu(II)-(CyHH)2 with glutathione or N-acetylcysteine was found only at a Cu(II)(CyHH)2/glutathione or Cu(II)(CyHH)2/N-acetylcysteine ratio of 1. The DNA strand scission caused by reaction mixtures of Cu(II) complexes with reductants was investigated under the same conditions as the ESR spin-trapping experiments. Addition of ascorbic acid to mixtures of these four Cu(II) complexes and DNA resulted in DNA strand breakage. Hydroquinone plus Cu(II)(CyHH)2 also caused DNA strand scission. In addition, DNA strand breakage was observed with the reaction of Cu(II)(OP)2 with glutathione, N-acetylcysteine, and hydroquinone. In contrast, reaction mixtures of glutathione, N-acetylcysteine, or hydroquinone with Cu(II)-(HGG) or Cu(II)(en)2 did not cause DNA strand scission within the concentration range used. The results obtained here suggest that there is a good correlation between POBN-CH3 formation and DNA strand scission. Thus, DNA strand scission may be caused by .OH generated from the reaction of some Cu(II) complexes with biological reductants under aerobic conditions. Since ascorbic acid, glutathione, and N-acetylcysteine are present in living cells, some Cu(II) complexes may be capable of initiating DNA damage in the presence of these reductants.

Authors+Show Affiliations

National Institute of Radiological Sciences, Chiba-shi, Japan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9735163

Citation

Ueda, J, et al. "Reactive Oxygen Species Generated From the Reaction of copper(II) Complexes With Biological Reductants Cause DNA Strand Scission." Archives of Biochemistry and Biophysics, vol. 357, no. 2, 1998, pp. 231-9.
Ueda J, Takai M, Shimazu Y, et al. Reactive oxygen species generated from the reaction of copper(II) complexes with biological reductants cause DNA strand scission. Arch Biochem Biophys. 1998;357(2):231-9.
Ueda, J., Takai, M., Shimazu, Y., & Ozawa, T. (1998). Reactive oxygen species generated from the reaction of copper(II) complexes with biological reductants cause DNA strand scission. Archives of Biochemistry and Biophysics, 357(2), 231-9.
Ueda J, et al. Reactive Oxygen Species Generated From the Reaction of copper(II) Complexes With Biological Reductants Cause DNA Strand Scission. Arch Biochem Biophys. 1998 Sep 15;357(2):231-9. PubMed PMID: 9735163.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reactive oxygen species generated from the reaction of copper(II) complexes with biological reductants cause DNA strand scission. AU - Ueda,J, AU - Takai,M, AU - Shimazu,Y, AU - Ozawa,T, PY - 1998/9/15/pubmed PY - 1998/9/15/medline PY - 1998/9/15/entrez SP - 231 EP - 9 JF - Archives of biochemistry and biophysics JO - Arch Biochem Biophys VL - 357 IS - 2 N2 - The generation of hydroxyl radicals (.OH) from the reaction of Cu(II) complexes with biological reductants such as ascorbic acid, glutathione, acetylcysteine, and hydroquinone was confirmed by spin-trapping experiments using electron spin resonance (ESR). The following Cu(II) complexes were used: Cu(II)-(CyHH)2 (CyHH, cyclo(L-histidyl-L-histidyl)), Cu(II)(OP)2 (OP, o-phenanthroline), Cu(II)(HGG) (HGG, L-histidyl-glycylglycine), and Cu(II)(en)2 (en, ethylenediamine). The methyl radical adduct of alpha-(pyridyl-4-N-oxide)-N-tert-butylnitrone (POBN-CH3) was obtained from the reaction of ascorbic acid with all Cu(II) complexes used here in the presence of a spin trap, POBN, and dimethyl sulfoxide, indicating the generation of .OH. Glutathione, N-acetylcysteine, and hydroquinone reacted with both Cu(II)(CyHH)2 and Cu(II)(OP)2 to generate POBN-CH3, while these reductants did not react with either Cu(II)(HGG) or Cu(II)(en)2. Interestingly, the formation of POBN-CH3 in the reaction of Cu(II)-(CyHH)2 with glutathione or N-acetylcysteine was found only at a Cu(II)(CyHH)2/glutathione or Cu(II)(CyHH)2/N-acetylcysteine ratio of 1. The DNA strand scission caused by reaction mixtures of Cu(II) complexes with reductants was investigated under the same conditions as the ESR spin-trapping experiments. Addition of ascorbic acid to mixtures of these four Cu(II) complexes and DNA resulted in DNA strand breakage. Hydroquinone plus Cu(II)(CyHH)2 also caused DNA strand scission. In addition, DNA strand breakage was observed with the reaction of Cu(II)(OP)2 with glutathione, N-acetylcysteine, and hydroquinone. In contrast, reaction mixtures of glutathione, N-acetylcysteine, or hydroquinone with Cu(II)-(HGG) or Cu(II)(en)2 did not cause DNA strand scission within the concentration range used. The results obtained here suggest that there is a good correlation between POBN-CH3 formation and DNA strand scission. Thus, DNA strand scission may be caused by .OH generated from the reaction of some Cu(II) complexes with biological reductants under aerobic conditions. Since ascorbic acid, glutathione, and N-acetylcysteine are present in living cells, some Cu(II) complexes may be capable of initiating DNA damage in the presence of these reductants. SN - 0003-9861 UR - https://www.unboundmedicine.com/medline/citation/9735163/Reactive_oxygen_species_generated_from_the_reaction_of_copper_II__complexes_with_biological_reductants_cause_DNA_strand_scission_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0003986198908116 DB - PRIME DP - Unbound Medicine ER -