Effect of carcinogenic acrolein on DNA repair and mutagenic susceptibility

Hsiang Tsui Wang, Yu Hu, Dan Tong, Jian Huang, Liya Gu, Xue Ru Wu, Fung Lung Chung, Guo Min Li, Moon Shong Tang

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Acrolein (Acr), a ubiquitous environmental contaminant, is a human carcinogen. Acr can react with DNA to form mutagenic α- and γ-hydroxy-1, N 2-cyclic propano-2′-deoxyguanosine adducts (α-OH-Acr-dG and γ-OH-Acr-dG). We demonstrate here that Acr-dG adducts can be efficiently repaired by the nucleotide excision repair (NER) pathway in normal human bronchial epithelia (NHBE) and lung fibroblasts (NHLF). However, the same adducts were poorly processed in cell lysates isolated from Acr-treated NHBE and NHLF, suggesting that Acr inhibits NER. In addition, we show that Acr treatment also inhibits base excision repair and mismatch repair. Although Acr does not change the expression of XPA, XPC, hOGG1, PMS2 or MLH1genes, it causes a reduction of XPA, XPC, hOGG1, PMS2, and MLH1 proteins; this effect, however, can be neutralized by the proteasome inhibitor MG132. Acr treatment further enhances both bulky and oxidative DNA damage-induced mutagenesis. These results indicate that Acr not only damages DNA but can also modify DNA repair proteins and further causes degradation of these modified repair proteins. We propose that these two detrimental effects contribute to Acr mutagenicity and carcinogenicity.

Original languageEnglish (US)
Pages (from-to)12379-12386
Number of pages8
JournalJournal of Biological Chemistry
Volume287
Issue number15
DOIs
StatePublished - Apr 6 2012

Fingerprint

Acrolein
DNA Repair
Repair
DNA
Fibroblasts
DNA Damage
Epithelium
Nucleotides
Lung
Mutagenesis
Proteins
Deoxyguanosine
Proteasome Inhibitors
DNA Mismatch Repair
Carcinogens

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Wang, H. T., Hu, Y., Tong, D., Huang, J., Gu, L., Wu, X. R., ... Tang, M. S. (2012). Effect of carcinogenic acrolein on DNA repair and mutagenic susceptibility. Journal of Biological Chemistry, 287(15), 12379-12386. https://doi.org/10.1074/jbc.M111.329623

Effect of carcinogenic acrolein on DNA repair and mutagenic susceptibility. / Wang, Hsiang Tsui; Hu, Yu; Tong, Dan; Huang, Jian; Gu, Liya; Wu, Xue Ru; Chung, Fung Lung; Li, Guo Min; Tang, Moon Shong.

In: Journal of Biological Chemistry, Vol. 287, No. 15, 06.04.2012, p. 12379-12386.

Research output: Contribution to journalArticle

Wang, HT, Hu, Y, Tong, D, Huang, J, Gu, L, Wu, XR, Chung, FL, Li, GM & Tang, MS 2012, 'Effect of carcinogenic acrolein on DNA repair and mutagenic susceptibility', Journal of Biological Chemistry, vol. 287, no. 15, pp. 12379-12386. https://doi.org/10.1074/jbc.M111.329623
Wang, Hsiang Tsui ; Hu, Yu ; Tong, Dan ; Huang, Jian ; Gu, Liya ; Wu, Xue Ru ; Chung, Fung Lung ; Li, Guo Min ; Tang, Moon Shong. / Effect of carcinogenic acrolein on DNA repair and mutagenic susceptibility. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 15. pp. 12379-12386.
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