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 journalArticlepeer-review

54 Scopus citations

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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