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

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.

Toll interacting protein protects bronchial epithelial cells from bleomycin‐induced apoptosis

“…To dissect the molecular mechanism of TOLLIP-mediated protection, we further analyzed the changes of apoptosis markers in a lung epithelial cell line, BEAS-2B, a widely used cell line for mechanistic studies of genes related to lung diseases. [39][40][41][42] Overexpression of the TOLLIP-V5 protein in BEAS-2B cells resulted in a time-dependent decrease of bleomycin-induced caspase-3 protein cleavage up to 12 hours ( Figure 3C,E). This effect was diminished at 16 hours when the TOLLIP-V5 expression was noticeably reduced.…”

Angiotensin‐converting enzyme 2: The old door for new severe acute respiratory syndrome coronavirus 2 infection

“…A, ACE2 expression data of 41 types of cancers obtained from The Cancer Genome Atlas (TCGA) database 104 ; mRNA expression z-score threshold was set at ±1.5. B, ACE2 expression in lung cancer patients with different smoking histories analyzed using similar methods as described previously 106 other symptoms in addition to respiratory symptoms, suggesting that SARS-CoV-2 could perhaps infect other organs (Figure 3). SARS-CoV-2 might infect other ACE2-expressing tissues via blood circulation as a recent report showed that SARS-CoV-2 RNA had been detected in the blood of some COVID-19 patients.…”

“…Indeed, increased risk of COVID-19 and poorer prognosis was observed in cancer patients. 105 In addition, using similar methods as described previously, 106 we compared the ACE2 expression in lung cancer patients of various smoking statuses.…”

The Impact of Coilin Nonsynonymous SNP Variants E121K and V145I on Cell Growth and Cajal Body Formation: The First Characterization

“…Cell growth was determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay according to the manufacturer’s protocol (Promega, Madison, WA, USA) and as described previously [ 26 ]. Briefly, the cells were seeded in 96-well plates at 1000 cells per well, and MTS assay was performed in a 12 h interval for up to 60 h.…”

“…Real-time quantitative PCR (RT-qPCR) was performed in order to examine the gene expression level of coilin using an ABI7500 Real-Time PCR System (Applied Biosystems, Foster City, CA, USA), and calculated using the comparative C T method as described previously [26]. Primers used are listed in Table S1.…”