Metabolic activation of carcinogenic ethylbenzene leads to oxidative DNA damage

Midorikawa, Katsumi; Uchida, Takafumi; Okamoto, Yoshinori; Toda, Chitose; Sakai, Yoshie; Ueda, Koji; Hiraku, Yusuke; Murata, Mariko; Kawanishi, Shosuke; Kojima, Nakao

doi:10.1016/j.cbi.2004.09.020

Cited by 42 publications

(16 citation statements)

References 35 publications

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“…It has been described that hexachlorobenzene is a genotoxic carcinogen and is able to produce a significant increase in micronuclei frequencies (36). Within this exposure-effect relationship, lower hexachlorobenzenerelated micronuclei levels were observed for individual carrying the mnSOD V 16 A variant and for individuals carrying the CYP1A1 T 3801 C variant alleles. The variant allele of the CYP1A1 T 3801 C genotype leads to an increase in CYP1A1 enzyme activity (37).…”

Section: Discussionmentioning

confidence: 96%

“…Of the investigated toxicants, only chlorobenzene and ethylbenzene were significantly associated with this biomarker; both associations have not yet been described in the literature. The main pathway of benzene biotransformation involves formation of metabolites that are known to generate reactive oxygen species through redox cycling (16,17). These reactive oxygen species eventually induce oxidative DNA damage; exposure to benzene in mice has been shown to induce oxidative DNA damage measured by the Comet assay (18,19).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, it has been shown both in rats (38) and in human breast tumors (39) that organochlorine pesticides such as hexachlorobenzene are associated with an increased oxidative stress. Regarding mnSOD, the mnSOD V 16 A variant is associated with a decrease in enzyme activity and, hence, an impaired antioxidant capacity against the oxidative metabolites produced during the metabolism of hexachlorobenzene. This is in contrast to what would be expected because less detoxification would lead to a higher accumulation of oxidative metabolites and, thus, higher micronuclei levels.…”

Section: Discussionmentioning

confidence: 99%

“…Within this relationship, 1.3 times higher micronuclei levels were observed in females compared with males (P < 0.001). Moreover, 0.9 times lower micronuclei levels were found in individuals with two variants for the mnSOD V 16 A genotype (P = 0.032) and for individuals carrying at least one variant for the CYP1A1 T 3801 C genotype (0.86 times for heterozygous individuals and 0.65 times for double variants; P = 0.001) compared with the respective wild-type genotypes.…”

Section: Cancer Epidemiology Biomarkers and Prevention Cancer Epidemiomentioning

confidence: 96%

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Multiplex Genotyping as a Biomarker for Susceptibility to Carcinogenic Exposure in the FLEHS Biomonitoring Study

Ketelslegers

Gottschalk

Koppen

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Cancer has been suggested to result from interactions between genetic and environmental factors, and certain subgroups in the general population may be at increased risk because of their relatively higher susceptibility to environmental carcinogens. The current study, part of a large biomonitoring study conducted in Flanders from 2002 to 2006 (The Flanders Environment and Health Survey), aims to determine these susceptible subpopulations based on multiple genotypic differences between individuals. A random selection of 429 adolescents and 361 adults was genotyped for 36 polymorphisms in 23 genes selected because of their known role in carcinogen metabolism, DNA repair, and oxidative stress. In both age groups, relationships between endogenous exposure to organochloride substances (polychlorinated biphenyl, hexachlorobenzene, dichlorodiphenyl dichloroethane), metals (cadmium, lead), and urinary metabolites (1-hydroxypyrene, trans-trans muconic acid) versus genotoxic effects (Comet assay and micronuclei in lymphocytes, and urinary 8-hydroxydeoxyguanosine) were investigated. In addition, in the study among adults, the relationship of these exposures with several tumor markers (prostate-specific antigen, carcinoembryonic antigen, and p53) was tested. The impact of the genotype on established exposure-effect relationships was evaluated. Eight exposure-effect relationships were found, including three novel associations, with an impact of various genotypes, predominantly affecting biotransformation and oxidative stress response. This study shows that at least part of the interindividual differences in relationships between carcinogen exposure and genotoxic effect can be explained by genotypic differences, enabling the identification of more susceptible subgroups for environmental cancer risks. This may be of relevance for environmental health policy setting. (Cancer Epidemiol Biomarkers Prev 2008;17(8):1902 -12)

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Cancer Epidemiology Biomarkers and Prevention Cancer Epidemiomentioning

confidence: 96%

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Multiplex Genotyping as a Biomarker for Susceptibility to Carcinogenic Exposure in the FLEHS Biomonitoring Study

Ketelslegers

Gottschalk

Koppen

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…3) Several groups including us proposed mechanisms for the oxidative DNA damage induced by copper and catechol compounds. 4,5) However, the detailed mechanisms remain to be elucidated. Followings are particularly concerned: damaging position on DNA (preferential vulnerability of consecutive guanines), the damaging forms of the reactive species, and physical distance between DNA and damaging factors.…”

Section: Introductionmentioning

confidence: 99%

Involvement of DNA Conformational Change Induced by Rearrangement of Copper-coordination Geometry in Oxidative DNA Damages Caused by Copper and Dopamine

Ando

Ueda

Makino

et al. 2009

JOURNAL OF HEALTH SCIENCE

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Oxidative DNA damages involve reductionoxidation reactions between certain metals and compounds, and result in genetic abnormalities leading to diseases including cancer and neurodegenerative disorders. Here, we report that DNA damages mediated by combination of a neurotransmitter dopamine and copper accompany a unique DNA conformational change. Copper(II) [Cu(II)] was shown as bound to consecutive guanines (G-G) of DNA, by demonstrating the G-G selective inhibition of restriction enzymes. When dopamine was added to calf thymus DNA in the presence of Cu(II), DNA guanines were oxidized. UV and 1 H NMR analyses suggested that dopamine was oxidized to the quinone form in the presence of Cu(II). The circular dichroism experiments showed DNA spectral changes under the conditions of oxidative DNA damage, indicating a conformational change of the DNA strand by dopamine and copper. The DNA conformational change was suppressed by adding a Cu(I)-specific chelator bathocuproine. Therefore, the conformational change can be explained by a rearrangement of the copper-coordination geometry in DNA through Cu(II) reduction to Cu(I). Thus, changes in DNA conformation could be involved in metal-mediated genotoxicity as well as oxidative damage but via different mechanism.

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Enhanced DNA Oxidative Damage by Acrylonitrile and Protecting DNA from Damage with an Outer Catalase Layer: an Electrochemical Study

Liu¹,

Hu²

2008

Electroanalysis

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In the present article, an in vitro model system to mimic the transformation of acrylonitrile (ACN) from nontoxic to toxic in DNA damage and the protective function of catalase (Cat) against DNA damage in real biosystems was investigated electrochemically with (CS/DNA) 3 -AQDS and (CS/DNA) 3 -AQDS-Cat multilayer films, where CS and AQDS represent chitosan and electroactive probe 9,10-anthraquinone-2,6-disulfonate, respectively. The electroactive AQDS was loaded into (CS/DNA) 3 layer-by-layer films mainly by intercalation of AQDS into the double-helix structure of DNA and acted as the probe to detect the damage of DNA in the films. While only ACN could not induce DNA damage, the enhancement of ACN on DNA damage in the presence of Fenton reagents (Fe(II)/EDTA/H 2 O 2 ) was observed. In addition, Cat in the (CS/DNA) 3 -AQDS-Cat films could protect DNA from damage to a considerable extent in both Fenton and Fenton þ ACN solutions because of the high efficiency of Cat in decomposition of H 2 O 2 .

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Metabolic activation of carcinogenic ethylbenzene leads to oxidative DNA damage

Cited by 42 publications

References 35 publications

Multiplex Genotyping as a Biomarker for Susceptibility to Carcinogenic Exposure in the FLEHS Biomonitoring Study

Multiplex Genotyping as a Biomarker for Susceptibility to Carcinogenic Exposure in the FLEHS Biomonitoring Study

Involvement of DNA Conformational Change Induced by Rearrangement of Copper-coordination Geometry in Oxidative DNA Damages Caused by Copper and Dopamine

Enhanced DNA Oxidative Damage by Acrylonitrile and Protecting DNA from Damage with an Outer Catalase Layer: an Electrochemical Study

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