Serial review: oxidative DNA damage and repairThe role of metals in site-specific DNA damage with reference to carcinogenesis1, 2
Introduction
A number of metals have carcinogenic potentials. The mechanism of metal carcinogenesis has been extensively investigated. In 1986, we proposed the hypothesis that metal carcinogenesis involves endogenous reactive oxygen species (ROS) generation (Fig. 1), since we discovered that chromium (VI), which has been confirmed to be a human carcinogen, induced oxidative DNA damage in the presence of hydrogen peroxide (H2O2) [1]. Thereafter, we have reported that various carcinogenic metal compounds are capable of causing oxidative DNA damage in the presence of H2O2 [2], [3], [4], [5]. This hypothesis has been supported by a number of studies on oxidative DNA damage in vivo induced by carcinogenic metal compounds. These metal compounds showed different site specificity depending on reactive species causing DNA damage. In addition, we have also found that lead and nickel compounds can induce site-specific DNA damage in vivo through indirect mechanisms.
Metals are considered to act as not only carcinogens but also co-carcinogens that activate carcinogenic chemicals. We have also demonstrated that a number of organic carcinogens induce oxidative DNA damage through metal-catalyzed ROS generation. Here we discuss the mechanisms of (i) metal carcinogenesis through oxidative DNA damage and (ii) the role of metals, particularly copper and iron, in carcinogenesis induced by aromatic hydrocarbons and aromatic nitro and amino compounds through oxidative DNA damage.
Section snippets
Metal carcinogenesis
Carcinogenic risks of metal compounds to humans have been evaluated by the International Agency for Research on Cancer (IARC). Chromium (VI), nickel (II), beryllium, cadmium, and arsenic compounds have been confirmed to be human carcinogens. Cobalt (II) and ferric nitrilotriacetate [Fe(III)-NTA] have shown carcinogenic effects in animal studies and are possibly carcinogenic to humans [6]. We found that DNA damage could be induced by carcinogenic metal compounds through ROS generation. On the
The role of metals in chemical carcinogenesis
We demonstrated that a large part of weakly mutagenic and nonmutagenic carcinogens appear to induce carcinogenesis through metal-mediated oxidative DNA damage. Particularly, endogenous metal ions, such as copper and iron, play an important role in ROS generation from various carcinogens, leading to DNA damage. In view of the very tightly controlled physiological uptake and turnover of copper and iron, it is difficult to consider any presence of free copper and iron ions available for the
Role of oxidative DNA damage in chemical carcinogenesis
We have investigated the mechanism of metal-induced carcinogenesis and the role of metals in carcinogenesis induced by various organic chemicals. Transition metal ions catalyze the formation of highly reactive species causing DNA damage, and its site specificity is determined by the chemical property of reactive species. Therefore, metal-catalyzed ROS generation may play a critical role for carcinogenesis induced by a wide variety of chemicals in humans. It is generally accepted that DNA adduct
References (110)
- et al.
Mechanism of DNA cleavage induced by sodium chromate(VI) in the presence of hydrogen peroxide
J. Biol. Chem.
(1986) - et al.
ESR evidence for superoxide, hydroxyl radicals, and singlet oxygen produced from hydrogen peroxide and nickel(II) complex of gylcylgylcyl-L-histidine
Biochem. Biophys. Res. Commum.
(1989) Carcinogenicity of metal compoundspossible role of DNA repair inhibition
Toxicol. Lett.
(1998)- et al.
Inhibition of 8-hydroxyguanine repair in testes after administration of cadmium chloride to GSH-depleted rats
Toxicol. Appl. Pharmacol.
(1997) - et al.
Oxidative DNA damage in cultured cells and rat lungs by carcinogenic nickel compounds
Free Radic. Biol. Med.
(2001) Carcinogen-mediated oxidant formation and oxidative DNA damage
Pharmacol. Ther.
(1992)- et al.
Sequencing end-labeled DNA with base-specific chemical cleavages
Methods Enzymol.
(1980) - et al.
DNA fragmentation, DNA-protein crosslinks, postlabeled nucleotidic modifications, and 8-hydroxy-2′-deoxyguanosine in the lung but not in the liver of rats receiving intratracheal instillations of chromium(VI). Chemoprevention by oral N-acetylcysteine
Mutat. Res.
(1998) - et al.
Urinary excretion of biomarkers of oxidative kidney damage induced by ferric nitrilotriacetate
Toxicol. Sci.
(1998) - et al.
Chronic infections and inflammatory processes as cancer risk factorspossible role of chronically elevated nitric oxide in carcinogenesis
Mutat. Res.
(1994)
Potential genotoxicity of chronically elevated nitric oxidea review
Mutat. Res.
Effects of ionic strength on endogenous nuclease activity in chelated and nonchelated chromatin
J. Inorg. Biochem.
Copper and genomic stability in mammals
Mutat. Res.
Hydroxyl free radical is not the main active species in site-specific DNA damage induced by copper (II) ion and hydrogen peroxide
J. Biol. Chem.
Superoxide dismutases enhance H2O2-induced DNA damage and alter its site specificity
FEBS Lett.
Binding and the nature of Cu(II) ion interaction with nucleosomes
J. Inorg. Biochem.
Iron and its sensitive balance in the cell
Mutat Res.
Role of iron and superoxide for generation of hydroxyl radical, oxidative DNA lesions, and mutagenesis in Escherichia coli
J. Biol. Chem.
Ferritin stimulation of hydroxy radical production by rat liver nuclei
Arch. Biochem. Biophys.
Role of active oxygen species in DNA damage by pentachlorophenol metabolites
Mutat. Res.
Oxidative DNA damage by minor metabolites of toluene may lead to carcinogenesis and reproductive dysfunction
Biochem. Biophys. Res. Commun.
Oxidative DNA damage and apoptosis induced by metabolites of butylated hydroxytoluene
Biochem. Pharmacol.
Oxidative DNA damage induced by homogentisic acid, a tyrosine metabolite
FEBS Lett.
Immunochemical, 32P-postlabeling, and GC/MS detection of 4-aminobiphenyl-DNA adducts in human peripheral lung in relation to metabolic activation pathways involving pulmonary N-oxidation, conjugation, and peroxidation
Mutat. Res.
Organ-specific genotoxicity of the potent rodent bladder carcinogens o-anisidine and p-cresidine
Mutat. Res.
Oxidative DNA damage by a metabolite of carcinogenic and reproductive toxic nitrobenzene in the presence of NADH and Cu(II)
Biochem. Biophys. Res. Commun.
Distinct mechanisms of oxidative DNA damage by two metabolites of carcinogenic o-toluidine
Arch. Biochem. Biophys.
Oxidative DNA damage induced by a metabolite of carcinogenic o-anisidineenhancement of DNA damage and alteration in its sequence-specificity by superoxide dismutase
Arch Biochem. Biophys.
Mutagenicity of 4-aminobiphenyl and 4-acetylaminobiphenyl in Salmonella typhimurium strains expressing different levels of N-acetyltransferase
Toxicol. Appl. Pharmacol.
Mechanism of oxidative DNA damage induced by carcinogenic 4-aminobiphenyl
Free Radic. Biol. Med.
Mechanism of metal-mediated DNA damage induced by metabolites of carcinogenic 2-nitropropane
Mutat. Res.
High production of catalase in hydrogen peroxide-resistant human leukemia HL-60 cell lines
Leuk. Res.
Benzoyl peroxide-induced damage to DNA and its componentsdirect evidence for the generation of base adducts, sugar radicals, and strand breaks
Arch. Biochem. Biophys.
Hydroxy radical production human DNA damage induced by ferric nitrilotriacetate hydrogen peroxide
Cancer Res.
Site-specific DNA damage induced by cobalt(II) ion and hydrogen peroxiderole of singlet oxygen
Chem. Res. Toxicol.
Site-specific DNA damage induced by nickel(II) ion in the presence of hydrogen peroxide
Carcinogenesis
Nephrotoxicity and renal cell carcinoma after use of iron- and aluminum-nitrilotriacetate complexes in rats
J. Natl. Cancer Inst.
Thiol involvement in the inhibition of DNA repair by metals in mammalian cells
Mol. Toxicol.
Epidemiological and experimental aspects of metal carcinogenesisphysicochemical properties, kinetics, and the active species
Environ. Health Perspect.
Mechanism of oxidative DNA damage induced by δ-aminolevulinic acid in the presence of copper ion
Cancer Res.
Possible role of oxidative damage in metal-induced carcinogenesis
Cancer Invest.
Chromium and chromium compounds
Complete nucleotide sequences of the T24 human bladder carcinoma oncogene and its normal homologue
Nature
Iron(II)-ethylenediaminetetraacetic acid catalyzed cleavage of RNA and DNA oligonucleotidessimilar reactivity toward single- and double-stranded forms
Biochemistry
Site-specific DNA damage induced by UVA radiation in the presence of endogenous photosensitizer
Biol. Chem.
The formation of DNA cleaving species during the reduction of chromate by ascorbate
Carcinogenesis
The formation of both apurinic/apyrimidinic sites and single-strand breaks by chromate and glutathione arises from attack by the same single reactive species and is dependent on molecular oxygen
Carcinogenesis
Body iron stores and the risk of cancer
N. Engl. J. Med.
Hydroxyl radical production and human DNA damage induced by ferric nitrilotriacetate and hydrogen peroxide
Cancer Res.
Iron-induced oxidative DNA damage and its repair in primary rat hepatocyte culture
Carcinogenesis.
Cited by (243)
Improved rRNA extraction from biofouling and bioreactor samples
2022, International Biodeterioration and BiodegradationRelative bioefficacy of seventeen Poaceae extracts targeting oxidative stress-related diseases coupled with elemental profiling using ICP-MS
2022, South African Journal of BotanyThe impacts of coal dust on miners’ health: A review
2020, Environmental ResearchPhotocatalytic and therapeutic applications of the synthesized nickle oxide (NiO) nanoparticles
2023, Journal of the Iranian Chemical Society
- 1
Guest Editor: Miral Dizdaroglu
- 2
This article is part of a series of reviews on “Oxidative DNA Damage and Repair.” The full list of papers may be found on the homepage of the journal.