Cadmium delays non-homologous end joining (NHEJ) repair via inhibition of DNA-PKcs phosphorylation and downregulation of XRCC4 and Ligase IV

Li, Weiwei; Gu, Xueyan; Zhang, Xiaoning; Kong, Jinxin; Ding, Nan; Qi, Yongmei; Zhang, Yingmei; Wang, Jufang; Huang, Dejun

doi:10.1016/j.mrfmmm.2015.07.002

Cited by 17 publications

(12 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Unlike previous studies where most DNA repair genes were reported to be suppressed upon acute or chronic Cd exposure [4,6,7,8,13,29,30], up-regulation of 10 out of 12 DNA repair genes in this study suggests that acute/chronic and post-chronic Cd-exposed cells have different transcriptomic landscapes of DNA repair. Most importantly, the DNA repair transcriptome of the CR0 cells also suggests that chronic Cd exposure has long-term effects on the expression of DNA repair-related genes in human lung cells.…”

Section: Resultscontrasting

confidence: 95%

“…However, as for the dsDNA damage repair, only four ( GADD45A , H2AFX , LIG3 , and REV1 ) genes were involved in the HRR and none for the NHEJ. These findings are remarkably similar with available literature where the evidence for Cd interference in BER, NER, and MMR is overwhelming, but not much on the repair of dsDNA breaks involving HRR and NHEJ [4,5,6].…”

Section: Resultssupporting

confidence: 89%

“…Previously, the expression of many important DNA repair genes (e.g., CRY1 , ERCC1 , LIG4 , MLH1 , MSH2 , MSH6 , MSH7 , OGG1 , PCNA , RAD21 , RAD50 , XRCC1 , and XRCC4 ) in human, animal, or plant cells were found to be suppressed by Cd [6,8,13,29,30]. In Zhou et al, the overexpression of DNA methyltransferase genes ( DNMT1 and DNMT3a ) resulted in the silencing of DNA repair genes ( MSH2 , ERCC1 , XRCC1 , and OGG1 ) in CdCl 2 -transformed human bronchial epithelial 16HBE cells and tumorigenic cells isolated from a xenograft nude mouse model [7].…”

Section: Discussionmentioning

confidence: 99%

“…Cd has the ability to alter the expression of various DNA repair genes, and it is known to be able to impair DNA repair system via down-regulation of DNA repair genes expression [6,7], suppression of transcription factor activity [8], and disruption of protein’s function by binding to its zinc finger motif [4,9]. Interestingly, so far, evidence of Cd interference is overwhelmingly available only for the repair pathways of single-stranded DNA (ssDNA) damage (e.g., base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR)), but very limited for double-stranded DNA (dsDNA) damage such as homologous recombinational repair (HRR) and non-homologous end-joining (NHEJ).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Tan

Liang

Yao

et al. 2019

Cells

View full text Add to dashboard Cite

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.

show abstract

Section: Resultscontrasting

confidence: 95%

Section: Resultssupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Tan

Liang

Yao

et al. 2019

Cells

View full text Add to dashboard Cite

show abstract

“…Meanwhile, Zn decreased the toxic effect of Cd on DDR pathway. 298 Overall, it seems that exposure to Cd leads to induction of genomic instability by influencing the mediators of the DDR/repair mechanism. Furthermore, Cd-mediated inhibition of apoptosis results in accumulation of unrepaired DNA damage in cells, which increases the mutation rate and probably progressing cancer-related genomic instability.…”

Section: Implicationmentioning

confidence: 99%

The crosstalk between trace elements with DNA damage response, repair, and oxidative stress in cancer

Tehrani

Hosseini

Yousefi

et al. 2018

J of Cellular Biochemistry

View full text Add to dashboard Cite

DNA damage response (DDR) is a regulatory system responsible for maintaining genome integrity and stability, which can sense and transduce DNA damage signals. The severity of damage appears to determine DDRs, which can include damage repair, cell‐cycle arrest, and apoptosis. Furthermore, defective components in DNA damage and repair machinery are an underlying cause for the development and progression of various types of cancers. Increasing evidence indicates that there is an association between trace elements and DDR/repair mechanisms. In fact, trace elements seem to affect mediators of DDR. Besides, it has been revealed that oxidative stress (OS) and trace elements are associated with cancer development. In this review, we discuss the role of some critical trace elements in the risk of cancer. In addition, we provide a brief introduction on DDR and OS in cancer. Finally, we will further review the interactions between some important trace elements including selenium, zinc, chromium, cadmium, and arsenic, and DDR, and OS in cancer.

show abstract

Temporal analysis of lung injury induced by real‐ambient PM₂_.5 exposure in mice

Zeng,

Chen,

et al. 2023

Environmental Toxicology

View full text Add to dashboard Cite

Fine particulate matter (PM2.5) has been shown to induce lung injury. However, the pathophysiological mechanisms of PM2.5‐induced pulmonary injury after different exposure times are poorly understood. In this study, we exposed male ICR mice to a whole‐body PM2.5 inhalation system at daily mean concentration range from 92.00 to 862.00 μg/m3 for 30, 60, and 90 days. We found that following prolonged exposure to PM2.5, pulmonary injury was increasingly evident with significant histopathological alterations. Notably, the pulmonary inflammatory response and fibrosis caused by PM2.5 after different exposure times were closely associated with histopathological changes. In addition, PM2.5 exposure caused oxidative stress, DNA damage and impairment of DNA repair in a time‐dependent manner in the lung. Importantly, exposure to PM2.5 eventually caused apoptosis in the lung through upregulation of cleaved‐caspase‐3 and downregulation of Bcl‐2. Overall, our data demonstrated that PM2.5 led to pulmonary injury in a time‐dependent manner via upregulation of proinflammatory and fibrosis‐related genes, and activation of the DNA damage response. Our findings provided a novel perspective on the pathophysiology of respiratory diseases caused by airborne pollution.

show abstract

Cadmium delays non-homologous end joining (NHEJ) repair via inhibition of DNA-PKcs phosphorylation and downregulation of XRCC4 and Ligase IV

Cited by 17 publications

References 41 publications

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

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

The crosstalk between trace elements with DNA damage response, repair, and oxidative stress in cancer

Temporal analysis of lung injury induced by real‐ambient PM₂_.5 exposure in mice

Contact Info

Product

Resources

About

Cadmium delays non-homologous end joining (NHEJ) repair via inhibition of DNA-PKcs phosphorylation and downregulation of XRCC4 and Ligase IV

Cited by 17 publications

References 41 publications

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

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

The crosstalk between trace elements with DNA damage response, repair, and oxidative stress in cancer

Temporal analysis of lung injury induced by real‐ambient PM2.5 exposure in mice

Contact Info

Product

Resources

About

Temporal analysis of lung injury induced by real‐ambient PM₂_.5 exposure in mice