Interaction of copper with DNA and antagonism by other metals

Sagripanti, José-Luis; Goering, Peter L.; Lamanna, Anthony

doi:10.1016/0041-008x(91)90048-j

Cited by 125 publications

(74 citation statements)

References 19 publications

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“…25 The necessity of Cu(II) for DNA damage has been identified by previous studies. 26,27 In this study, physiological concentrations of copper (20 M) 28 and NADH (100 M) 29 mediated DNA damage induced by catechol estrogens, suggesting that the DNA damage could be relevant to physiological conditions. Thus, catechol estrogens could play important roles in tumor initiation by causing oxidative DNA damage, whereas estradiol itself does not contribute to initiation.…”

Section: Discussionmentioning

confidence: 54%

Catechol estrogens induce oxidative DNA damage and estradiol enhances cell proliferation

et al. 2001

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Estrogen-induced carcinogenesis involves enhanced cell proliferation (promotion) and genotoxic effects (initiation).To investigate the contribution of estrogens and their metabolites to tumor initiation, we examined DNA damage induced by estradiol and its metabolites, the catechol estrogens 2-hydroxyestradiol (2-OHE 2 ) and 4-hydroxyestradiol (4-OHE 2 ). In the presence of Cu(II), catechol estrogens formed piperidine-labile sites at thymine and cytosine residues in 32 P 5 -end-labeled DNA fragments and induced the formation of 8-oxo-7, Epidemiological studies and animal experiments have revealed that estrogens are carcinogenic. 1 In humans, elevated circulating estrogen levels, caused either by increased endogenous hormone production or by therapeutic doses of estrogen medications, increase breast and uterine cancer risk. 2 Prolonged exposure of women to high estrogen levels is associated with an elevated incidence of breast cancer. 3 Administration of estradiol to mice increased the incidence of mammary, pituitary, uterine, cervical, vaginal, testicular, lymphoid and bone tumors. 2,4 In rats, estrogen increased the incidence of mammary and/or pituitary tumors. 2,5 Estrogens can cause cancer by stimulating cell proliferation and causing genotoxic damage. 6,7 Estrogens are highly mitogenic in hormone-sensitive tissues, such as the uterus and breast. 8 Prolonged exposure of target tissues and cells to excessive mitogenic stimulation by estrogens has been considered an important etiological factor for the induction of estrogen-associated cancers in experimental animals and humans. 8 Thus, estrogens are considered to participate in tumor promotion.However, estrogens have been reported to cause cancer through their genotoxic effects. Estradiol caused sister chromatid exchanges and chromosomal aberrations in peripheral blood human lymphocyte culture, and metabolic activation enhanced these chromosomal lesions. 9 Catechol estrogens are also capable of causing chromosomal aberrations and gene mutations in cultured cells. 10 Thus, the genotoxic effects of estradiol could result from accumulation of potentially carcinogenic metabolites. Estradiol undergoes cytochrome P-450 -catalyzed hydroxylation to various catechol estrogens. 8 2-Hydroxylation is a major metabolic pathway in the liver, whereas 4-hydroxylation dominates in extrahepatic organs susceptible to estrogens. 8,11,12 Catechol estrogens show much more potent carcinogenic effects on mice than estradiol. 13 Therefore, catechol estrogens can be potent carcinogens and may participate in tumor initiation by causing DNA damage.To investigate the role of catechol estrogens in tumor initiation, we examined DNA damage induced by 2-hydroxyestradiol (2-OHE 2 ) and 4-hydroxyestradiol (4-OHE 2 ) using 32 P 5Ј-end-labeled DNA fragments obtained from the human p53 tumor-suppressor gene and the c-Ha-ras-1 proto-oncogene. We also measured the formation of 8-oxo-7,8-dihydro-2Ј-deoxyguanosine (8-oxodG), an indicator of oxidative damage to DNA, using an electrochemical detector coup...

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Section: Discussionmentioning

confidence: 54%

Catechol estrogens induce oxidative DNA damage and estradiol enhances cell proliferation

et al. 2001

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“…Furthermore, to clarify the mechanism of cellular DNA damage, we examined the DNA damage caused by catechol in the presence of metal ions, using 32 P-5'-end-labeled DNA fragments obtained from the human p16 and p53 tumor suppressor genes and the c-Ha-ras-1 protooncogene. Catechol caused damage to DNA fragments in the presence of physiological concentration of Cu(II) (20 μM) (21). When 100 μM NADH was added, the DNA damage was markedly enhanced and clearly observed in relatively low concentrations of catechol (<1 μM).…”

Section: The Role Of Reactive Oxygen Species In Carcinogenesismentioning

confidence: 99%

Sequence-specific DNA damage by reactive oxygen species: Implications for carcinogenesis and aging

Oikawa

2005

Environ Health Prev Med

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Reactive oxygen species (ROS) generated by environmental chemicals can cause sequence-specific DNA damage, which may lead to carcinogenesis and aging. We investigated the mechanism of DNA damage by environmental chemicals (catechol, propyl gallate and bisphenol-A), homocysteine and UVA radiation using human cultured cell lines and 32 P-labeled DNA fragments. Carcinogenic catechol induced piperidine-labile sites frequently at thymine residues in the presence of Cu(II) and NADH. Furthermore, catechol increased the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a characteristic oxidative DNA lesion, in human leukemia cell line HL-60, but not in HP100, a hydrogen peroxide (H 2 O 2 )-resistant cell line derived from HL-60. Thus, it is concluded that oxidative DNA damage through generation of H 2 O 2 plays an important role in the carcinogenic process of catechol. In addition, an environmental factor, bisphenol-A, and a dietary factor, propyl gallate, also induced sequence-specific DNA damage via ROS generation.UVA, as well as UVB, contributes to photoaging. In humans, telomere shortening is believed to be associated with cell senescence. In this study, we investigated the shortening rate of telomeres in human WI-38 fibroblasts exposed to UVA irradiation. The telomere length (as measured by terminal restriction fragment length) in WI-38 fibroblasts irradiated with UVA decreased with increasing the irradiation dose. UVA irradiation with riboflavin caused damage specifically at the GGG sequence in the DNA fragments containing telomere sequence (TTAGGG) 4 . We concluded that the GGG-specific damage in telomere sequence induced by UVA irradiation participates in the increase of the telomere shortening rate.In this report, we show our experimental results and discuss the mechanisms of sequence-specific DNA damage in relation to carcinogenesis and aging.

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“…Copper can also directly bind to protein sulfhydryl and amino groups, leading to structural and functional modifications (13,30,38,41,68). Finally, copper can bind to DNA to form adducts and is involved in chromatin condensation (11,58). Thus, it is critical for organisms to maintain homeostatic concentrations of copper, because abnormally high or low levels can lead to pathological conditions (8).…”

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confidence: 99%

Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper

Song

Freedman

2009

Physiological Genomics

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Copper is an essential trace element; however, at supraphysiological levels, it can be extremely toxic. Microarray data from HepG2 cells exposed to 100, 200, 400, and 600 μM copper for 4, 8, 12 and 24 h were generated and analyzed. Principal components, K-means, and hierarchical clustering, interactome, and pathway mapping analyses indicated that these exposure conditions induce physiological and toxicological changes in the HepG2 transcriptome. As a general trend, when the level of toxicity increases, the number and diversity of affected genes, Gene Ontology categories, regulatory pathways, and complexity of interactomes increase. Physiological responses to copper include transition metal ion binding and responses to stress/stimulus, whereas toxicological responses include apoptosis, morphogenesis, and negative regulation of biomolecule metabolism. The global gene expression profile was overlaid onto biomolecular interaction networks and signal transduction cascades using pathway mapping and interactome identification. This analysis indicated that copper modulates signal transduction pathways associated with MAPK, NF-κB, death receptor, IGF-I, hypoxia, IL-10, IL-2, IL-6, EGF, Toll-like receptor, protein ubiquitination, xenobiotic metabolism, leukocyte extravasation, complement and coagulation, and sonic hedgehog signaling. These results provide insights into the global and molecular mechanisms regulating the physiological and toxicological responses to metal exposure.

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Interaction of copper with DNA and antagonism by other metals

Cited by 125 publications

References 19 publications

Catechol estrogens induce oxidative DNA damage and estradiol enhances cell proliferation

Catechol estrogens induce oxidative DNA damage and estradiol enhances cell proliferation

Sequence-specific DNA damage by reactive oxygen species: Implications for carcinogenesis and aging

Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper

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