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Cells. 2019 Aug 6;8(8). pii: E842. doi: 10.3390/cells8080842.

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

Tan HW1, Liang ZL1, Yao Y1, Wu DD1,2,3, Mo HY1, Gu J4,5,6, Chiu JF7, Xu YM8,9,10, Lau ATY11,12,13.

Author information

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.
8
Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou 515041, Guangdong, China. amyymxu@stu.edu.cn.
9
Provincial Key Laboratory of Infectious Diseases and Molecular Pathology, Shantou University Medical College, Shantou 515041, Guangdong, China. amyymxu@stu.edu.cn.
10
Collaborative and Creative Center of Molecular Pathology and Personalized Medicine, Shantou University Medical College, Shantou 515041, Guangdong, China. amyymxu@stu.edu.cn.
11
Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou 515041, Guangdong, China. andytylau@stu.edu.cn.
12
Provincial Key Laboratory of Infectious Diseases and Molecular Pathology, Shantou University Medical College, Shantou 515041, Guangdong, China. andytylau@stu.edu.cn.
13
Collaborative and Creative Center of Molecular Pathology and Personalized Medicine, Shantou University Medical College, Shantou 515041, Guangdong, China. andytylau@stu.edu.cn.

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.

KEYWORDS:

BEAS-2B; DNA damage and repair; cadmium; carcinogenesis; cell transformation; drug sensitivity; human lung cells; post-chronic exposure

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