Lasting DNA Damage and Aberrant DNA Repair Gene Expression Profile Are Associated with Post-Chronic Cadmium Exposure in Human Bronchial Epithelial Cells
Abstract
:1. Introduction
2. Materials and Methods
2.1. Establishment of Chronic and Post-Chronic Cd-Exposed Human Bronchial Epithelial BEAS-2B Cell Models
2.2. Determination of Cell Proliferation and Cell Viability
2.3. Detection of DNA Damage and DNA Repair Capacity
2.4. Determination of Colony Formation Ability
2.5. Detection of Histone H2AFX and γH2AFX Expression
2.6. Assessment of Global DNA Repair-Related Gene Expression Profile
2.7. Analysis of Clinical Data Obtained from Online Databases
2.8. Statistical Analysis
3. Results
3.1. Establishment of a Post-Chronic Cd-Exposed BEAS-2B Cell Line (the “CR0” Cells)
3.2. Cd-Resistant Cells Retain Cd Tolerance Feature for an Extended Period of Time
3.3. Exposure to Cd Resulted in Cells Having Lasting DNA Damage and Reduced DNA Repair Capacity
3.4. Aberrant Expression of DNA Repair Gene Profile Is Associated with Post-Chronic Cd Exposure
3.5. Short-Term Cd Exposure Reveals Different DNA Repair Transcriptomic Landscapes in Normal and Cd-Exposed Cells
3.6. Clinical Database Analysis of Lung Cancer Samples with Different Smoking Histories
3.7. Post-Chronic Cd Exposure Resulted in Cells Having Reduced DNA Repair Capacity and More Susceptible to Chemotherapy
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Acronym | DNA Repair Pathways | No. of Genes 1 | Gene Name (UniProtKB accession ID) |
---|---|---|---|
Major DNA Repair Pathways | |||
BER | Base excision repair | 38 | APEX1 (P27695); CCNO (P22674); ERCC1 (P07992); ERCC4 (Q92889); ERCC5 (P28715); ERCC6 (Q03468); FEN1 (P39748); GADD45A (P24522); HUS1 (O60921); LIG1 (P18858); LIG3 (P49916); MBD4 (O95243); MPG (P29372); MUTYH (Q9UIF7); NEIL1 (Q96FI4); NEIL2 (Q969S2); NEIL3 (Q8TAT5); NTHL1 (P78549); OGG1 (O15527); PARP1 (P09874); PARP2 (Q9UGN5); PARP3 (Q9Y6F1); PCNA (P12004); POLB (P06746); POLD3 (Q15054); RAD23A (P54725); RAD23B (P54727); RAD52 (P43351); RPA1 (P27694); RPA2 (P15927); RPA3 (P35244); SIRT1 (Q96EB6); SMUG1 (Q53HV7); TDG (Q13569); TP53 (P04637); UNG (P13051); WRN (Q14191); XRCC1 (P18887) |
NER | Nucleotide excision repair | 37 | ATR (Q13535); ATXN3 (P54252); CCNH (P51946); CDK7 (P50613); CETN2 (P41208); DDB1 (Q16531); DDB2 (Q92466); ERCC1 (P07992); ERCC2 (P18074); ERCC3 (P19447); ERCC4 (Q92889); ERCC5 (P28715); ERCC6 (Q03468); ERCC8 (Q13216); GADD45A (P24522); GTF2H1 (P32780); GTF2H2 (Q13888); GTF2H3 (Q13889); GTF2H4 (Q92759); LIG1 (P18858); LIG3 (P49916); MMS19 (Q96T76); NTHL1 (P78549); OGG1 (O15527); PCNA (P12004); POLD3 (Q15054); RAD23A (P54725); RAD23B (P54727); RFC1 (P35251); RPA1 (P27694); RPA2 (P15927); RPA3 (P35244); SIRT1 (Q96EB6); TP53 (P04637); XAB2 (Q9HCS7); XPA (P23025); XRCC1 (P18887) |
MMR | Mismatch repair | 19 | ABL1 (P00519); EXO1 (Q9UQ84); MLH1 (P40692); MLH3 (Q9UHC1); MSH2 (P43246); MSH3 (P20585); MSH4 (O15457); MSH5 (O43196); MSH6 (P52701); PCNA (P12004); PMS1 (P54277); PMS2 (P54278); POLD3 (Q15054); RFC1 (P35251); RPA1 (P27694); RPA2 (P15927); RPA3 (P35244); TDG (Q13569); TREX1 (Q9NSU2) |
HRR | Homologous recombinational repair | 49 | ATM (Q13315); ATR (Q13535); BLM (P54132); BRCA1 (P38398); BRCA2 (P51587); BRIP1 (Q9BX63); CHEK1 (O14757); DMC1 (Q14565); ERCC1 (P07992); ERCC4 (Q92889); ERCC6 (Q03468); FANCA (O15360); FANCB (Q8NB91); FANCF (Q9NPI8); FANCG (O15287); FEN1 (P39748); GADD45A (P24522); H2AFX (P16104); HUS1 (O60921); LIG3 (P49916); MDC1 (Q14676); MRE11 (P49959); MSH2 (P43246); MSH4 (O15457); MSH5 (O43196); MSH6 (P52701); NBN (O60934); PARP1 (P09874); PARP2 (Q9UGN5); PARP3 (Q9Y6F1); RAD17 (O75943); RAD21 (O60216); RAD50 (Q92878); RAD51 (Q06609); RAD51B (O15315); RAD51C (O43502); RAD51D (O75771); RAD52 (P43351); RAD54B (Q9Y620); RAD54L (Q92698); REV1 (Q9UBZ9); RPA1 (P27694); RPA2 (P15927); RPA3 (P35244); SIRT1 (Q96EB6); TP53BP1 (Q12888); WRN (Q14191); XRCC1 (P18887); XRCC2 (O43543) |
NHEJ | Non-homologous end-joining | 22 | ATM (Q13315); ATP23 (Q9Y6H3); BRCA1 (P38398); ERCC1 (P07992); ERCC4 (Q92889); LIG4 (P49917); MDC1 (Q14676); MLH1 (P40692); MRE11 (P49959); NBN (O60934); PARP1 (P09874); PARP2 (Q9UGN5); PARP3 (Q9Y6F1); PRKDC (P78527); RAD50 (Q92878); SIRT1 (Q96EB6); TP53BP1 (Q12888); WRN (Q14191); XRCC1 (P18887); XRCC4 (Q13426); XRCC5 (P13010); XRCC6 (P12956) |
Other DNA Repair Pathways | |||
POL | Polymerases | 4 | PCNA (P12004); POLB (P06746); POLD3 (Q15054); REV1 (Q9UBZ9) |
DRD | Direct reversal of damage | 3 | ALKBH1 (Q13686); ALKBH3 (Q96Q83); MGMT (P16455) |
SMNP | Sanitization/modulation of nucleotide pools | 3 | DUT (P33316); NUDT1 (P36639); RRM2B (Q7LG56) |
FA | Fanconi anemia | 9 | BRCA1 (P38398); BRCA2 (P51587); BRIP1 (Q9BX63); FANCA (O15360); FANCB (Q8NB91); FANCF (Q9NPI8); FANCG (O15287); RAD51 (Q06609); RAD51C (O43502) |
TLM | Telomere maintenance | 26 | ATR (Q13535); BRCA1 (P38398); BRCA2 (P51587); ERCC1 (P07992); ERCC4 (Q92889); FEN1 (P39748); MRE11 (P49959); NBN (O60934); PARP1 (P09874); PARP3 (Q9Y6F1); PCNA (P12004); POLD3 (Q15054); RAD50 (Q92878); RAD51 (Q06609); RAD51C (O43502); RAD51D (O75771); RFC1 (P35251) RPA1 (P27694); RPA2 (P15927); RPA3 (P35244); SIRT1 (Q96EB6); TP53 (P04637); WRN (Q14191); XRCC1 (P18887); XRCC5 (P13010); XRCC6 (P12956) |
TLS | Translesion synthesis | 3 | PCNA (P12004); POLD3 (Q15054); REV1 (Q9UBZ9) |
CSM | Chromatin structure and modification | 16 | CHEK1 (O14757); ERCC6 (Q03468); FEN1 (P39748); H2AFX (P16104); LIG3 (P49916); PCNA (P12004); RAD17 (O75943); RAD21 (O60216); RAD51 (Q06609); RAD51C (O43502); RPA1 (P27694); RPA2 (P15927); RPA3 (P35244); SIRT1 (Q96EB6); TP53 (P04637); XRCC1 (P18887) |
MMEJR | Microhomology-mediated end-joining repair | 6 | FEN1 (P39748); LIG3 (P49916); MRE11 (P49959); NBN (O60934); PARP1 (P09874); XRCC1 (P18887) |
SDA | Genes defective in diseases associated with sensitivity to DNA-damaging agents | 7 | ATM (Q13315); ATXN3 (P54252); BLM (P54132); ERCC6 (Q03468); ERCC8 (Q13216); NBN (O60934); WRN (Q14191) |
UBM | Ubiquitination and modification (Rad6 pathways) | 6 | RAD18 (Q9NS91); SHPRH (Q149N8); UBE2A (P49459); UBE2B (P63146); UBE2N (P61088); UBE2V2 (Q15819) |
OTHER | Other DNA damage-related | 4 | CRY1 (Q16526); SUMO1 (P63165); TOP3A (Q13472); TOP3B (O95985) |
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Tan, H.W.; Liang, Z.-L.; Yao, Y.; Wu, D.-D.; Mo, H.-Y.; Gu, J.; Chiu, J.-F.; Xu, Y.-M.; Lau, A.T.Y. Lasting DNA Damage and Aberrant DNA Repair Gene Expression Profile Are Associated with Post-Chronic Cadmium Exposure in Human Bronchial Epithelial Cells. Cells 2019, 8, 842. https://doi.org/10.3390/cells8080842
Tan HW, Liang Z-L, Yao Y, Wu D-D, Mo H-Y, Gu J, Chiu J-F, Xu Y-M, Lau ATY. Lasting DNA Damage and Aberrant DNA Repair Gene Expression Profile Are Associated with Post-Chronic Cadmium Exposure in Human Bronchial Epithelial Cells. Cells. 2019; 8(8):842. https://doi.org/10.3390/cells8080842
Chicago/Turabian StyleTan, Heng Wee, Zhan-Ling Liang, Yue Yao, Dan-Dan Wu, Hai-Ying Mo, Jiang Gu, Jen-Fu Chiu, Yan-Ming Xu, and Andy T. Y. Lau. 2019. "Lasting DNA Damage and Aberrant DNA Repair Gene Expression Profile Are Associated with Post-Chronic Cadmium Exposure in Human Bronchial Epithelial Cells" Cells 8, no. 8: 842. https://doi.org/10.3390/cells8080842