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Open AccessArticle

Lasting DNA Damage and Aberrant DNA Repair Gene Expression Profile Are Associated with Post-Chronic Cadmium Exposure in Human Bronchial Epithelial Cells

1
Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou 515041, Guangdong, China
2
Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
3
GRIAC Research Institute, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
4
Provincial Key Laboratory of Infectious Diseases and Molecular Pathology, Shantou University Medical College, Shantou 515041, Guangdong, China
5
Collaborative and Creative Center of Molecular Pathology and Personalized Medicine, Shantou University Medical College, Shantou 515041, Guangdong, China
6
Department of Pathology and Pathophysiology, Shantou University Medical College, Shantou 515041, Guangdong, China
7
School of Biomedical Sciences, LKS Faculty of Medicine, University of Hong Kong, Hong Kong, China
*
Authors to whom correspondence should be addressed.
Cells 2019, 8(8), 842; https://doi.org/10.3390/cells8080842
Received: 27 June 2019 / Revised: 28 July 2019 / Accepted: 2 August 2019 / Published: 6 August 2019
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Abstract

Cadmium (Cd) is a widespread environmental pollutant and carcinogen. Although the exact mechanisms of Cd-induced carcinogenesis remain unclear, previous acute/chronic Cd exposure studies have shown that Cd exerts its cytotoxic and carcinogenic effects through multiple mechanisms, including interference with the DNA repair system. However, the effects of post-chronic Cd exposure remain unknown. Here, we establish a unique post-chronic Cd-exposed human lung cell model (the “CR0” cells) and investigate the effects of post-chronic Cd exposure on the DNA repair system. We found that the CR0 cells retained Cd-resistant property even though it was grown in Cd-free culture medium for over a year. The CR0 cells had lasting DNA damage due to reduced DNA repair capacity and an aberrant DNA repair gene expression profile. A total of 12 DNA repair genes associated with post-chronic Cd exposure were identified, and they could be potential biomarkers for identifying post-chronic Cd exposure. Clinical database analysis suggests that some of the DNA repair genes play a role in lung cancer patients with different smoking histories. Generally, CR0 cells were more sensitive to chemotherapeutic (cisplatin, gemcitabine, and vinorelbine tartrate) and DNA damaging (H2O2) agents, which may represent a double-edged sword for cancer prevention and treatment. Overall, we demonstrated for the first time that the effects of post-chronic Cd exposure on human lung cells are long-lasting and different from that of acute and chronic exposures. Findings from our study unveiled a new perspective on Cd-induced carcinogenesis—the post-chronic exposure of Cd. This study encourages the field of post-exposure research which is crucial but has long been ignored. View Full-Text
Keywords: cadmium; post-chronic exposure; DNA damage and repair; BEAS-2B; human lung cells; cell transformation; carcinogenesis; drug sensitivity cadmium; post-chronic exposure; DNA damage and repair; BEAS-2B; human lung cells; cell transformation; carcinogenesis; drug sensitivity
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Tan, H.W.; Liang, Z.-L.; Yao, Y.; Wu, D.-D.; Mo, H.-Y.; Gu, J.; Chiu, J.-F.; Xu, Y.-M.; Lau, A.T.Y. Lasting DNA Damage and Aberrant DNA Repair Gene Expression Profile Are Associated with Post-Chronic Cadmium Exposure in Human Bronchial Epithelial Cells. Cells 2019, 8, 842.

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