Nickel accumulation in lung tissues is associated with increased risk of p53 mutation in lung cancer patients

Yu Hu Chiou, Ruey Hong Wong, Mu Rong Chao, Chih Yi Chen, Saou Hsing Liou, Huei Lee

研究成果: 雜誌貢獻文章

16 引文 (Scopus)

摘要

Occupational exposure to nickel compounds has been associated with lung cancer. The correlation between high nickel levels and increased risk of lung cancer has been previously reported in a case-control study. This study assessed whether nickel exposure increased the occurrence of p53 mutations due to DNA repair inhibition by nickel. A total of 189 lung cancer patients were enrolled to determine nickel levels in tumor-adjacent normal lung tissues and p53 mutation status in lung tumors through atomic absorption spectrometry and direct sequencing, respectively. Nickel levels in p53 mutant patients were significantly higher than those in p53 wild-type patients. When patients were divided into high- and low-nickel subgroups by median nickel level, the high-nickel subgroup of patients had an odds ratio (OR) of 3.25 for p53 mutation risk relative to the low-nickel subgroup patients. The OR for p53 mutation risk of lifetime non-smokers, particularly females, in the high-nickel subgroup was greater than that in the low-nickel subgroup. To determine whether nickel affected DNA repair capacity, we conducted the host cell reactivation assay in A549 and H1975 lung cancer cells and showed that the DNA repair activity was reduced by nickel chloride in a dose-dependent manner. This was associated with elevated production of hydrogen peroxide-induced 8-oxo-deoxyguanosine. Therefore, increased risk of p53 mutation due to defective DNA repair caused by high nickel levels in lung tissues may be one mechanism by which nickel exposure contributes to lung cancer development, especially in lifetime female non-smokers.
原文英語
頁(從 - 到)624-632
頁數9
期刊Environmental and Molecular Mutagenesis
55
發行號8
DOIs
出版狀態已發佈 - 十月 1 2014

指紋

Nickel
Lung Neoplasms
Lung
Mutation
DNA Repair
Odds Ratio
Deoxyguanosine
Occupational Exposure
Hydrogen Peroxide
Case-Control Studies
Neoplasms
Spectrum Analysis

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Epidemiology
  • Genetics(clinical)
  • Medicine(all)

引用此文

Nickel accumulation in lung tissues is associated with increased risk of p53 mutation in lung cancer patients. / Chiou, Yu Hu; Wong, Ruey Hong; Chao, Mu Rong; Chen, Chih Yi; Liou, Saou Hsing; Lee, Huei.

於: Environmental and Molecular Mutagenesis, 卷 55, 編號 8, 01.10.2014, p. 624-632.

研究成果: 雜誌貢獻文章

Chiou, Yu Hu ; Wong, Ruey Hong ; Chao, Mu Rong ; Chen, Chih Yi ; Liou, Saou Hsing ; Lee, Huei. / Nickel accumulation in lung tissues is associated with increased risk of p53 mutation in lung cancer patients. 於: Environmental and Molecular Mutagenesis. 2014 ; 卷 55, 編號 8. 頁 624-632.
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abstract = "Occupational exposure to nickel compounds has been associated with lung cancer. The correlation between high nickel levels and increased risk of lung cancer has been previously reported in a case-control study. This study assessed whether nickel exposure increased the occurrence of p53 mutations due to DNA repair inhibition by nickel. A total of 189 lung cancer patients were enrolled to determine nickel levels in tumor-adjacent normal lung tissues and p53 mutation status in lung tumors through atomic absorption spectrometry and direct sequencing, respectively. Nickel levels in p53 mutant patients were significantly higher than those in p53 wild-type patients. When patients were divided into high- and low-nickel subgroups by median nickel level, the high-nickel subgroup of patients had an odds ratio (OR) of 3.25 for p53 mutation risk relative to the low-nickel subgroup patients. The OR for p53 mutation risk of lifetime non-smokers, particularly females, in the high-nickel subgroup was greater than that in the low-nickel subgroup. To determine whether nickel affected DNA repair capacity, we conducted the host cell reactivation assay in A549 and H1975 lung cancer cells and showed that the DNA repair activity was reduced by nickel chloride in a dose-dependent manner. This was associated with elevated production of hydrogen peroxide-induced 8-oxo-deoxyguanosine. Therefore, increased risk of p53 mutation due to defective DNA repair caused by high nickel levels in lung tissues may be one mechanism by which nickel exposure contributes to lung cancer development, especially in lifetime female non-smokers.",
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