Increased formation of hepatic N2 -ethylidene-2′-deoxyguanosine DNA adducts in aldehyde dehydrogenase 2-knockout mice treated with ethanol

Tomonari Matsuda, Akiko Matsumoto, Mitsuhiro Uchida, Robert A. Kanaly, Kentaro Misaki, Shinya Shibutani, Toshihiro Kawamoto, Kyoko Kitagawa, Keiichi Nakayama, Katsumaro Tomokuni, Masayoshi Ichiba

研究成果: ジャーナルへの寄稿記事

51 引用 (Scopus)

抄録

N2-ethylidene-2′-deoxyguanosine (N2 -ethylidene-dG) is a major DNA adduct induced by acetaldehyde. Although it is unstable in the nucleoside form, it is relatively stable when present in DNA. In this study, we analyzed three acetaldehyde-derived DNA adducts, N2-ethylidene-dG, N2-ethyl-2′-deoxyguanosine (N2-Et-dG) and α-methyl-γ-hydroxy-1, N2 -propano-2′-deoxyguanosine (α-Me-γ-OH-PdG) in the liver DNA of aldehyde dehydrogenase (Aldh)-2-knockout mice to determine the influence of alcohol consumption and the Aldh2 genotype on the levels of DNA damage. In control Aldh2+/+ mice, the level of N2-ethylidene-dG adduct in liver DNA was 1.9 ± 0.7 adducts per 107 bases and was not significantly different than that of Aldh2+/- and -/- mice. In alcohol-fed mice (20% ethanol for 5 weeks), the adduct levels of Aldh2+/+, +/- and -/- mice were 7.9 ± 1.8, 23.3 ± 4.0 and 79.9 ± 14.2 adducts per 107 bases, respectively, and indicated that adduct level was alcohol and Aldh2 genotype dependent. In contrast, an alcohol- or Aldh2 genotype-dependent increase was not observed for α-Me-γ-OH-PdG, and N2-Et-dG was not detected in any of the analyzed samples. In conclusion, the risk of formation of N2-ethylidene-dG in model animal liver in vivo is significantly higher in the Aldh2-deficient population and these results may contribute to our understanding of in vivo adduct formation in humans.

元の言語英語
ページ(範囲)2363-2366
ページ数4
ジャーナルCarcinogenesis
28
発行部数11
DOI
出版物ステータス出版済み - 11 1 2007

Fingerprint

Aldehyde Dehydrogenase
DNA Adducts
Knockout Mice
Ethanol
Acetaldehyde
Liver
Genotype
Alcohols
DNA
Nucleosides
Alcohol Drinking
DNA Damage
Animal Models
N2-ethylidene-2'-deoxyguanosine
Population
N2-ethyl-2'-deoxyguanosine
hydroxide ion

All Science Journal Classification (ASJC) codes

  • Cancer Research

これを引用

Matsuda, T., Matsumoto, A., Uchida, M., Kanaly, R. A., Misaki, K., Shibutani, S., ... Ichiba, M. (2007). Increased formation of hepatic N2 -ethylidene-2′-deoxyguanosine DNA adducts in aldehyde dehydrogenase 2-knockout mice treated with ethanol. Carcinogenesis, 28(11), 2363-2366. https://doi.org/10.1093/carcin/bgm057

Increased formation of hepatic N2 -ethylidene-2′-deoxyguanosine DNA adducts in aldehyde dehydrogenase 2-knockout mice treated with ethanol. / Matsuda, Tomonari; Matsumoto, Akiko; Uchida, Mitsuhiro; Kanaly, Robert A.; Misaki, Kentaro; Shibutani, Shinya; Kawamoto, Toshihiro; Kitagawa, Kyoko; Nakayama, Keiichi; Tomokuni, Katsumaro; Ichiba, Masayoshi.

:: Carcinogenesis, 巻 28, 番号 11, 01.11.2007, p. 2363-2366.

研究成果: ジャーナルへの寄稿記事

Matsuda, T, Matsumoto, A, Uchida, M, Kanaly, RA, Misaki, K, Shibutani, S, Kawamoto, T, Kitagawa, K, Nakayama, K, Tomokuni, K & Ichiba, M 2007, 'Increased formation of hepatic N2 -ethylidene-2′-deoxyguanosine DNA adducts in aldehyde dehydrogenase 2-knockout mice treated with ethanol', Carcinogenesis, 巻. 28, 番号 11, pp. 2363-2366. https://doi.org/10.1093/carcin/bgm057
Matsuda, Tomonari ; Matsumoto, Akiko ; Uchida, Mitsuhiro ; Kanaly, Robert A. ; Misaki, Kentaro ; Shibutani, Shinya ; Kawamoto, Toshihiro ; Kitagawa, Kyoko ; Nakayama, Keiichi ; Tomokuni, Katsumaro ; Ichiba, Masayoshi. / Increased formation of hepatic N2 -ethylidene-2′-deoxyguanosine DNA adducts in aldehyde dehydrogenase 2-knockout mice treated with ethanol. :: Carcinogenesis. 2007 ; 巻 28, 番号 11. pp. 2363-2366.
@article{f50e0852cc4344faa2511080852cd956,
title = "Increased formation of hepatic N2 -ethylidene-2′-deoxyguanosine DNA adducts in aldehyde dehydrogenase 2-knockout mice treated with ethanol",
abstract = "N2-ethylidene-2′-deoxyguanosine (N2 -ethylidene-dG) is a major DNA adduct induced by acetaldehyde. Although it is unstable in the nucleoside form, it is relatively stable when present in DNA. In this study, we analyzed three acetaldehyde-derived DNA adducts, N2-ethylidene-dG, N2-ethyl-2′-deoxyguanosine (N2-Et-dG) and α-methyl-γ-hydroxy-1, N2 -propano-2′-deoxyguanosine (α-Me-γ-OH-PdG) in the liver DNA of aldehyde dehydrogenase (Aldh)-2-knockout mice to determine the influence of alcohol consumption and the Aldh2 genotype on the levels of DNA damage. In control Aldh2+/+ mice, the level of N2-ethylidene-dG adduct in liver DNA was 1.9 ± 0.7 adducts per 107 bases and was not significantly different than that of Aldh2+/- and -/- mice. In alcohol-fed mice (20{\%} ethanol for 5 weeks), the adduct levels of Aldh2+/+, +/- and -/- mice were 7.9 ± 1.8, 23.3 ± 4.0 and 79.9 ± 14.2 adducts per 107 bases, respectively, and indicated that adduct level was alcohol and Aldh2 genotype dependent. In contrast, an alcohol- or Aldh2 genotype-dependent increase was not observed for α-Me-γ-OH-PdG, and N2-Et-dG was not detected in any of the analyzed samples. In conclusion, the risk of formation of N2-ethylidene-dG in model animal liver in vivo is significantly higher in the Aldh2-deficient population and these results may contribute to our understanding of in vivo adduct formation in humans.",
author = "Tomonari Matsuda and Akiko Matsumoto and Mitsuhiro Uchida and Kanaly, {Robert A.} and Kentaro Misaki and Shinya Shibutani and Toshihiro Kawamoto and Kyoko Kitagawa and Keiichi Nakayama and Katsumaro Tomokuni and Masayoshi Ichiba",
year = "2007",
month = "11",
day = "1",
doi = "10.1093/carcin/bgm057",
language = "English",
volume = "28",
pages = "2363--2366",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "11",

}

TY - JOUR

T1 - Increased formation of hepatic N2 -ethylidene-2′-deoxyguanosine DNA adducts in aldehyde dehydrogenase 2-knockout mice treated with ethanol

AU - Matsuda, Tomonari

AU - Matsumoto, Akiko

AU - Uchida, Mitsuhiro

AU - Kanaly, Robert A.

AU - Misaki, Kentaro

AU - Shibutani, Shinya

AU - Kawamoto, Toshihiro

AU - Kitagawa, Kyoko

AU - Nakayama, Keiichi

AU - Tomokuni, Katsumaro

AU - Ichiba, Masayoshi

PY - 2007/11/1

Y1 - 2007/11/1

N2 - N2-ethylidene-2′-deoxyguanosine (N2 -ethylidene-dG) is a major DNA adduct induced by acetaldehyde. Although it is unstable in the nucleoside form, it is relatively stable when present in DNA. In this study, we analyzed three acetaldehyde-derived DNA adducts, N2-ethylidene-dG, N2-ethyl-2′-deoxyguanosine (N2-Et-dG) and α-methyl-γ-hydroxy-1, N2 -propano-2′-deoxyguanosine (α-Me-γ-OH-PdG) in the liver DNA of aldehyde dehydrogenase (Aldh)-2-knockout mice to determine the influence of alcohol consumption and the Aldh2 genotype on the levels of DNA damage. In control Aldh2+/+ mice, the level of N2-ethylidene-dG adduct in liver DNA was 1.9 ± 0.7 adducts per 107 bases and was not significantly different than that of Aldh2+/- and -/- mice. In alcohol-fed mice (20% ethanol for 5 weeks), the adduct levels of Aldh2+/+, +/- and -/- mice were 7.9 ± 1.8, 23.3 ± 4.0 and 79.9 ± 14.2 adducts per 107 bases, respectively, and indicated that adduct level was alcohol and Aldh2 genotype dependent. In contrast, an alcohol- or Aldh2 genotype-dependent increase was not observed for α-Me-γ-OH-PdG, and N2-Et-dG was not detected in any of the analyzed samples. In conclusion, the risk of formation of N2-ethylidene-dG in model animal liver in vivo is significantly higher in the Aldh2-deficient population and these results may contribute to our understanding of in vivo adduct formation in humans.

AB - N2-ethylidene-2′-deoxyguanosine (N2 -ethylidene-dG) is a major DNA adduct induced by acetaldehyde. Although it is unstable in the nucleoside form, it is relatively stable when present in DNA. In this study, we analyzed three acetaldehyde-derived DNA adducts, N2-ethylidene-dG, N2-ethyl-2′-deoxyguanosine (N2-Et-dG) and α-methyl-γ-hydroxy-1, N2 -propano-2′-deoxyguanosine (α-Me-γ-OH-PdG) in the liver DNA of aldehyde dehydrogenase (Aldh)-2-knockout mice to determine the influence of alcohol consumption and the Aldh2 genotype on the levels of DNA damage. In control Aldh2+/+ mice, the level of N2-ethylidene-dG adduct in liver DNA was 1.9 ± 0.7 adducts per 107 bases and was not significantly different than that of Aldh2+/- and -/- mice. In alcohol-fed mice (20% ethanol for 5 weeks), the adduct levels of Aldh2+/+, +/- and -/- mice were 7.9 ± 1.8, 23.3 ± 4.0 and 79.9 ± 14.2 adducts per 107 bases, respectively, and indicated that adduct level was alcohol and Aldh2 genotype dependent. In contrast, an alcohol- or Aldh2 genotype-dependent increase was not observed for α-Me-γ-OH-PdG, and N2-Et-dG was not detected in any of the analyzed samples. In conclusion, the risk of formation of N2-ethylidene-dG in model animal liver in vivo is significantly higher in the Aldh2-deficient population and these results may contribute to our understanding of in vivo adduct formation in humans.

UR - http://www.scopus.com/inward/record.url?scp=34547120224&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547120224&partnerID=8YFLogxK

U2 - 10.1093/carcin/bgm057

DO - 10.1093/carcin/bgm057

M3 - Article

C2 - 17361010

AN - SCOPUS:34547120224

VL - 28

SP - 2363

EP - 2366

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 11

ER -