Lipid peroxidation-induced DNA adducts in human gastric mucosa

Matsuda, Tomonari; Hong, Tao; Goto, Masanori; Yamada, Hidetaka; Suzuki, Mitsuaki; Wu, Yijia; Xiao, Nong; He, Qiong; Guo, Wenwen; Cai, Zhenming; Kurabe, Nobuya; Ishino, Keiko; Matsushima, Yoshitaka; Shinmura, Kazuya; Konno, Hiroyuki; Maekawa, Masato; Wang, Yaping; Sugimura, Haruhiko

doi:10.1093/carcin/bgs327

Cited by 60 publications

(49 citation statements)

References 34 publications

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“…46,47 Consistent with this observation, structurally analogous N-(2,3,4-trihydroxy-butyl)valine (THB-Val) hemoglobin adducts have been detected in control subjects with no known exposure to BD. 48 Similarly, DNA adducts such as N7-methylguanine, 49 N7-ethylguanine, 31 1, N 2 -etheno-2′-deoxyguanosine, 50,51 1, N 2 -propanodeoxyguanosine, 52 etheno adducts such as 1, N 6 -ethenodeoxyadenosine (εdA), heptanone-etheno-2′-deoxyguanosine, 53 and 3, N 4 -ethenodeoxycytine (εdC) are also endogenously found in human DNA. 54,55 …”

Section: Discussionmentioning

confidence: 99%

Capillary HPLC-Accurate Mass MS/MS Quantitation of N7-(2,3,4-Trihydroxybut-1-yl)-guanine Adducts of 1,3-Butadiene in Human Leukocyte DNA

Sangaraju

Villalta

Goggin

et al. 2013

Chem. Res. Toxicol.

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1,3-butadiene (BD) is a high volume industrial chemical commonly used in polymer and rubber production. It is also present in cigarette smoke, automobile exhaust, and urban air, leading to widespread exposure of human populations. Upon entering the body, BD is metabolized to electrophilic epoxides, 3,4-epoxy-1-butene (EB), diepoxybutane (DEB), and 3,4-epoxy-1,2-diol (EBD), which can alkylate DNA nucleobases. The most abundant BD epoxide, EBD, modifies the N7-guanine positions in DNA to form N7-(2, 3, 4-trihydroxybut-1-yl) guanine (N7-THBG) adducts, which can be useful as biomarkers of BD exposure and metabolic activation to DNA-reactive epoxides. In the present work, a capillary HPLC- high resolution ESI+-MS/MS (HPLC-ESI+-HRMS/MS) methodology was developed for accurate, sensitive, and reproducible quantification of N7-THBG in cell culture and in human white blood cells. In our approach, DNA is subjected to neutral thermal hydrolysis to release N7-guanine adducts from the DNA backbone, followed by ultrafiltration, solid phase extraction, and isotope dilution HPLC-ESI+-HRMS/MS analysis on an Orbitrap Velos mass spectrometer. Following method validation, N7-THBG was quantified in human fibrosarcoma (HT1080) cells treated with μmolar concentrations of DEB and in DNA isolated from blood of smokers, nonsmokers, individuals participating in a smoking cessation program, and occupationally exposed workers. N7-THBG concentrations increased linearly from 31.4μ± 4.84 to 966.55 ± 128.05 adducts per 109 nucleotides in HT1080 cells treated with 1 -100 μM DEB. N7-THBG amounts in leukocyte DNA of non-smokers, smokers, and occupationally exposed workers were 7.08 ± 5.29, 8.20 ± 5.12, and 9.72 ± 3.80 adducts per 109 nucleotides, respectively, suggesting the presence of an endogenous or environmental source for this adduct. The availability of sensitive HPLC-ESI+-HRMS/MS methodology for BD-induced DNA adducts in humans will enable future population studies of inter-individual and ethnic differences in BD bioactivation to DNA-reactive epoxides.

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Section: Discussionmentioning

confidence: 99%

Capillary HPLC-Accurate Mass MS/MS Quantitation of N7-(2,3,4-Trihydroxybut-1-yl)-guanine Adducts of 1,3-Butadiene in Human Leukocyte DNA

Sangaraju

Villalta

Goggin

et al. 2013

Chem. Res. Toxicol.

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“…Matsuda and co-workers have published a series of investigations 20,35,36,72,74,75,80 after establishing a pseudo-CNL methodology. 35 They employed a triple quadrupole MS and acquired 32 SRM transitions per injection with 12 injections per sample to cover a mass range of m / z 228.8 to 602.8 amu.…”

Section: Dna Adductomics Analysis Using Mass Spectrometrymentioning

confidence: 99%

DNA Adductomics

Balbo

Turesky²,

Villalta³

2014

Chem. Res. Toxicol.

160

179

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Systems toxicology is a broad based approach to describe many of the toxicological features that occur within a living system under stress or subjected to exogenous or endogenous exposures. The ultimate goal is to capture an overview of all exposures and the ensuing biological responses of the body. The term “exposome” has been employed to refer to the totality of all exposures and systems toxicology investigates how the exposome influences health effects and consequences of exposures over a lifetime. The tools to advance systems toxicology include high-throughput transcriptomics, proteomics, metabolomics and adductomics, which is still in its infancy. A well-established methodology for the comprehensive measurement of DNA damage resulting from every day exposures is not fully developed. During the past several decades, the 32P-postlabeling technique has been employed to screen the damage to DNA induced by multiple classes of genotoxicants; however, more robust, specific, and quantitative methods have been sought to identify and quantify DNA adducts. While triple quadrupole and ion trap mass spectrometry, in particular when using multistage scanning (LC-MSn), have shown promise in the field of DNA adductomics, it is anticipated that high resolution and accurate mass LC-MSn instrumentation will play a major role in assessing global DNA damage. Targeted adductomics should benefit greatly from improved triple quadrupole technology. Once the analytical MS methods are fully mature, DNA adductomics along with other –omics tools will contribute greatly to the field of systems toxicology.

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“…Lipid peroxidation results in the production of lipid radicals and lipid peroxide, which in turn can propagate the formation of lipid radicals eventually altering the cell membrane, leading to modified proteins and DNA bases, mutagenic properties that have been shown to be carcinogenic [27–29]. …”

Section: Structure and Functionmentioning

confidence: 99%

Vitamin E: A dark horse at the crossroad of cancer management

Cárdenas

Ghosh²

2013

Biochemical Pharmacology

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It appears that the story on vitamin E and its role in human health remains incomplete. It is apparent that vitamin E supplementation involves many variables, some of which include its uptake from the intestine, the preference for α-tocopherol, transport by tocopherol specific proteins and lipid transporters and the differential metabolism of different vitamin E isoforms. The fundamental differences within population genetics can have significant implications for the effect that dietary supplementation might have on human health. When evaluating the efficacy of vitamin E prophylactic or therapeutic use in previous and future studies, it is critical to consider dosage to be administered, form of vitamin E and source (such as whether from synthetic or purified from natural sources). Further studies are needed to determine the effects of all vitamin E isoforms on cell growth, tumorigenicity, to clarify its possible use as an adjuvant to existing chemotherapeutics. The Alpha-Tocopherol, Beta Carotene (ATBC) Cancer Prevention Study Group and Selenium and Vitamin E Cancer Prevention Trial (SELECT) studies along with the numerous studies of vitamin E should help guide the next chapter of vitamin E research.

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Lipid peroxidation-induced DNA adducts in human gastric mucosa

Cited by 60 publications

References 34 publications

Capillary HPLC-Accurate Mass MS/MS Quantitation of N7-(2,3,4-Trihydroxybut-1-yl)-guanine Adducts of 1,3-Butadiene in Human Leukocyte DNA

Capillary HPLC-Accurate Mass MS/MS Quantitation of N7-(2,3,4-Trihydroxybut-1-yl)-guanine Adducts of 1,3-Butadiene in Human Leukocyte DNA

DNA Adductomics

Vitamin E: A dark horse at the crossroad of cancer management

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