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

• Published in: Cells (Basel, Switzerland) Switzerland), 2019-08, Vol.8 (8), p.842
• Main Authors: Tan, Heng Wee, Liang, Zhan-Ling, Yao, Yue, Wu, Dan-Dan, Mo, Hai-Ying, Gu, Jiang, Chiu, Jen-Fu, Xu, Yan-Ming, Lau, Andy T Y
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Air Pollutants - toxicity; BEAS-2B; Cadmium; Cadmium - toxicity; Carcinogenesis; Carcinoma, Squamous Cell - genetics; Cell culture; Cell growth; Cell Line; cell transformation; Cell Transformation, Neoplastic; Chronic exposure; Cisplatin; Cytotoxicity; Databases, Genetic; Deoxyribonucleic acid; DNA; DNA Damage; DNA damage and repair; DNA methylation; DNA repair; DNA Repair - genetics; drug sensitivity; Epithelial cells; Epithelial Cells - cytology; Epithelial Cells - metabolism; Experiments; Gemcitabine; Gene expression; human lung cells; Humans; Hydrogen peroxide; Lung - cytology; Lung - metabolism; Lung cancer; Lung Neoplasms - genetics; Pollutants; post-chronic exposure; Vinorelbine
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells8080842

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 (H O ) 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.