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

Heng Wee Tan, Zhan-Ling Liang, Yue Yao, Dan-Dan Wu, Hai-Ying Mo, Jiang Gu, Jen-Fu Chiu, Yan-Ming Xu, Andy T. Y. Lau

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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.

    Original languageEnglish
    Article number842
    Number of pages21
    JournalCells
    Volume8
    Issue number8
    DOIs
    Publication statusPublished - 6-Aug-2019

    Keywords

    • cadmium
    • post-chronic exposure
    • DNA damage and repair
    • BEAS-2B
    • human lung cells
    • cell transformation
    • carcinogenesis
    • drug sensitivity
    • REAL-TIME
    • MALIGNANT-TRANSFORMATION
    • LUNG
    • METHYLATION
    • MECHANISMS
    • CIGARETTE
    • PHOSPHORYLATION
    • INHIBITION
    • CHLORIDE
    • METALS

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