Role of Ape1 in Impaired DNA Repair Capacity in Battery Recycling Plant Workers Exposed to Lead
Abstract
:1. Introduction
2. Materials and Methods
2.1. Subjects
2.2. Sample Collection
2.3. Blood Lead Concentration
2.4. Delta-Aminolevulinic Acid Dehydratase Activity (δ-ALAD)
2.5. Lipid Peroxidation
2.6. DNA Damage (Comet Assay)
2.7. Irradiation Procedure
2.8. DNA Repair Capacity
2.9. cDNA Expression Array
2.10. Reverse-Transcriptase-Polymerase Chain Reaction (RT-PCR)
- APE1-F-TAATTCTCTATCTCTGCCCC
- APE1-R-CAGTAATTCCCCGAAGCCTT
- GAPDH-F-AAACGACCCCTTCATTGACCT
- GAPDH-R-ATCTTAGTGGGGTCTCGCTC
2.11. Cell Protein Extractions
2.12. Western Blot for Ape1
2.13. Ape1 Functional Assay
2.14. Statistical Analysis
3. Results
3.1. Lead Exposure and Oxidative Stress Markers
3.2. Occupational Lead Exposure Decreases DNA Repair Capacity
3.3. Expression Profile of Toxicity and Stress Genes in Workers Exposed to Lead
3.4. Impaired DNA Repair Capacity by APE1 in Lead Exposed Workers
3.5. In Silico Prediction of Transcription Factor Binding Sites
3.6. Interaction of Oxidative Markers of Lead Exposure and the Loss of Ape1 Activity in Exposed Workers
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variables | Non-Exposed (16) | Lead Exposed (37) |
---|---|---|
Age (years) | 37.15 ± 7.09 | 31.65 ± 8.56 |
Duration of exposed (years) | - | 4.53 ± 3.29 |
Smoking (%) | 18.70 | 16.00 |
Blood lead concentration (µg/dL) | 1.42 ± 0.87 | 69.25 ± 24.95 *** |
ALAD activity (nmol/mL/h) | 567.70 ± 46.20 | 312.86 ± 27.99 *** |
MDA (nmol/mL) | 0.87 ± 0.03 | 1.52 ± 0.08 |
# | Gene | Exposed/NonExposed | FC Log2 | t Test (p Value) | # | Gene | Exposed/Non Exposed | FC Log2 | t Test (p Value) | # | Gene | Exposed/Non Exposed | FC Long2 | t Test (p Value) |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | ANXAS | 1.361 | 0.445 | 0.180 | 38 | GSR | 0.583 | −0.778 | 0.001 | 75 | PTGS2 | 1.347 | 0.429 | 0.128 |
2 | ATM | 0.850 | −0.234 | 0.224 | 39 | GSTM3 | 0.649 | −0.623 | 0.005 | 76 | RAD23A | 1.307 | 0.386 | 0.146 |
3 | BAX | 1.374 | 0.459 | 0.132 | 40 | HMOX1 | 0.546 | −0.873 | 0.001 | 77 | RAD50 | 0.883 | −0.179 | 0.257 |
4 | BCL2L1 | 1.046 | 0.064 | 0.413 | 41 | HMOX2 | 1.807 | 0.853 | 0.072 | 78 | CCL21 | 0.759 | −0.397 | 0.073 |
5 | BCL2L2 | 0.868 | −0.204 | 0.254 | 42 | HSF1 | 1.689 | 0.756 | 0.050 | 79 | CCL3 | 0.799 | −0.324 | 0.161 |
6 | CASPS | 0.836 | −0.258 | 0.182 | 43 | HSPH1 | 1.162 | 0.216 | 0.306 | 80 | CCL4 | 0.609 | −0.716 | 0.013 |
7 | CASP10 | 0.862 | −0.215 | 0.257 | 44 | HSPA1A | 1.074 | 0.103 | 0.395 | 81 | CXCL10 | 1.728 | 0.789 | 0.012 |
8 | CASP8 | 0.660 | −0.599 | 0.036 | 45 | PTGS1 | 0.657 | −0.607 | 0.004 | 82 | SERPINE1 | 1.565 | 0.646 | 0.041 |
9 | CAT | 1.752 | 0.809 | 0.071 | 46 | HSPA1L | 0.601 | −0.734 | 0.000 | 83 | SOD1 | 1.373 | 0.457 | 0.067 |
10 | CCNC | 1.521 | 0.605 | 0.095 | 47 | HSPA2 | 0.684 | −0.548 | 0.017 | 84 | SOD2 | 0.910 | −0.135 | 0.246 |
11 | CCND1 | 1.280 | 0.356 | 0.210 | 48 | HSPA4 | 0.582 | −0.780 | 0.004 | 85 | TNF | 0.707 | −0.500 | 0.011 |
12 | CCNG1 | 0.902 | −0.149 | 0.346 | 49 | HSPA5 | 1.682 | 0.750 | 0.094 | 86 | TNFRSF1A | 0.807 | −0.309 | 0.156 |
13 | CDKN1A | 0.728 | −0.458 | 0.075 | 50 | HSPA6 | 1.699 | 0.764 | 0.065 | 87 | TNFSF10 | 0.718 | −0.478 | 0.067 |
14 | CHEK2 | 0.831 | −0.268 | 0.166 | 51 | HSPA8 | 1.150 | 0.202 | 0.297 | 88 | FASLG | 0.608 | −0.718 | 0.011 |
15 | CRYAB | 1.297 | 0.375 | 0.157 | 52 | HSPA9B | 0.937 | −0.093 | 0.411 | 89 | TP53 | 1.332 | 0.413 | 0.079 |
16 | CSF2 | 0.884 | −0.178 | 0.307 | 53 | HSPAB1 | 0.593 | −0.753 | 0.000 | 90 | TRADD | 1.439 | 0.525 | 0.017 |
17 | CYP1A1 | 1.495 | 0.580 | 0.120 | 54 | HSPCA | 0.577 | −0.792 | 0.000 | 91 | UGT1A4 | 0.841 | −0.250 | 0.167 |
18 | CYP1B1 | 1.638 | 0.712 | 0.086 | 55 | HSPCB | 0.709 | −0.495 | 0.013 | 92 | UNG | 0.676 | −0.565 | 0.007 |
19 | CYP2E1 | 1.142 | 0.191 | 0.349 | 56 | HSPD1 | 0.622 | −0.684 | 0.003 | 93 | XRCC1 | 0.638 | −0.648 | 0.000 |
20 | CYP7A1 | 0.837 | −0.256 | 0.283 | 57 | HSPE1 | 1.216 | 0.282 | 0.242 | 94 | XRCC2 | 0.745 | −0.424 | 0.073 |
21 | CYP7B1 | 0.714 | −0.486 | 0.052 | 58 | IGFBP6 | 1.774 | 0.827 | 0.044 | 95 | XRCC4 | 0.900 | −0.151 | 0.312 |
22 | DDB1 | 0.749 | −0.417 | 0.059 | 59 | IL1B | 0.976 | −0.036 | 0.462 | 96 | XRCC5 | 0.788 | −0.344 | 0.165 |
23 | DDIT3 | 0.959 | −0.061 | 0.430 | 60 | IL1A | 0.988 | −0.017 | 0.483 | 97 | PUC18 | 1.271 | 0.346 | 0.172 |
24 | DNA1A1 | 0.678 | −0.561 | 0.032 | 61 | 1L1B | 0.631 | −0.664 | 0.003 | 98 | PUC18 | 1.232 | 0.301 | 0.148 |
25 | DNAJB4 | 0.796 | −0.328 | 0.163 | 62 | 1L6 | 0.712 | −0.490 | 0.020 | 99 | PUC18 | 0.920 | −0.120 | 0.303 |
26 | E2F1 | 1.431 | 0.517 | 0.118 | 63 | LTA | 0.739 | −0.436 | 0.072 | 103 | GAPDH | 1.032 | 0.046 | 0.430 |
27 | EGR1 | 1.015 | 0.022 | 0.478 | 64 | MDM2 | 0.643 | −0.636 | 0.020 | 104 | GAPDH | 0.950 | −0.074 | 0.402 |
28 | EPHX2 | 0.749 | −0.417 | 0.175 | 65 | MIF | 1.607 | 0.684 | 0.072 | 109 | RPL13A | 0.837 | −0.256 | 0.117 |
29 | ERCC1 | 0.712 | −0.490 | 0.080 | 66 | PRDX1 | 1.928 | 0.947 | 0.020 | 110 | RPL13A | 0.875 | −0.193 | 0.289 |
30 | ERCC3 | 0.655 | −0.611 | 0.008 | 67 | PRDX2 | 1.314 | 0.394 | 0.078 | 111 | ACTB | 0.933 | −0.101 | 0.383 |
31 | ERCC4 | 0.640 | −0.643 | 0.007 | 68 | MT2A | 1.101 | 0.138 | 0.030 | 112 | ACTB | 0.868 | 0.204 | 0.280 |
32 | ERCC5 | 0.584 | −0.777 | 0.004 | 69 | NFKB1 | 0.770 | −0.377 | 0.060 | |||||
33 | FM01 | 1.274 | 0.350 | 0.210 | 70 | NFKB1A | 0.753 | −0.409 | 0.054 | |||||
34 | FM05 | 1.592 | 0.671 | 0.059 | 71 | NOS2A | 0.668 | −0.583 | 0.025 | |||||
35 | GADD45A | 1.013 | 0.019 | 0.482 | 72 | PCNA | 0.591 | −0.759 | 0.009 | |||||
36 | GADD5B | 1.053 | 0.074 | 0.427 | 73 | GDF15 | 1.915 | 0.937 | 0.028 | |||||
37 | GPX1 | 0.736 | −0.441 | 0.036 | 74 | POR | 1.924 | 0.944 | 0.010 |
Gene | Lead Exposed/Non Exposed | Fold Change log2 | t-Test (p Value) | Up/Down |
---|---|---|---|---|
HSPCA | 0.577 | −0.792 | 6.8 × 10−5 | Down |
HSPA4 | 0.582 | −0.780 | 0.004 | Down |
GSR | 0.583 | −0.778 | 0.001 | Down |
ERCC5 | 0.584 | −0.777 | 0.004 | Down |
PCNA | 0.591 | −0.759 | 0.009 | Down |
HSPB1 | 0.593 | −0.753 | 0.000 | Down |
HSPA1L | 0.601 | −0.734 | 0.000 | Down |
FASLG | 0.608 | −0.718 | 0.011 | Down |
CCL4 | 0.609 | −0.716 | 0.013 | Down |
HSPD1 | 0.622 | −0.684 | 0.003 | Down |
IL1B | 0.631 | −0.664 | 0.003 | Down |
XRCC1 | 0.638 | −0.648 | 0.000 | Down |
ERCC4 | 0.640 | −0.643 | 0.007 | Down |
MDM2 | 0.643 | −0.636 | 0.020 | Down |
GSTM3 | 0.649 | −0.623 | 0.005 | Down |
ERCC3 | 0.655 | −0.611 | 0.008 | Down |
PTGS1 | 0.657 | −0.607 | 0.004 | Down |
CASP8 | 0.660 | −0.599 | 0.036 | Down |
NOS2A | 0.668 | −0.583 | 0.025 | Down |
UNG | 0.676 | −0.565 | 0.007 | Down |
DNAJA1 | 0.678 | −0.561 | 0.032 | Down |
HSPA2 | 0.684 | −0.548 | 0.017 | Down |
TNF | 0.707 | −0.500 | 0.011 | Down |
HSPCB | 0.709 | −0.495 | 0.013 | Down |
IL6 | 0.712 | −0.490 | 0.020 | Down |
CYP7B1 | 0.714 | −0.486 | 0.050 | Down |
GPX1 | 0.736 | −0.441 | 0.036 | Down |
NFKBIA | 0.753 | −0.409 | 0.050 | Down |
SERPINE1 | 1.565 | 0.646 | 0.041 | Up |
HSF1 | 1.689 | 0.756 | 0.050 | Up |
CXCL10 | 1.728 | 0.789 | 0.012 | Up |
IGFBP6 | 1.774 | 0.827 | 0.044 | Up |
GDF15 | 1.915 | 0.937 | 0.028 | Up |
POR | 1.924 | 0.944 | 0.010 | Up |
PRDX1 | 1.928 | 0.947 | 0.030 | UP |
Transcription Factors Families | Predicted Number of Downregulated Target Genes | Predicted Number of DNA Repair Genes |
---|---|---|
CEBP (Basic leucine zipper factors (bZIP)) | 16 | 6 |
SOX (High/mobility group (HMG) domain | 16 | 13 |
HOX and POU (Home o domain factors) | 38 | 24 |
FOS (Basic leucine zipper factors (bZIP)) | 20 | 17 |
MYC (Basic helix-loop/helix factors (bHLH)) | 21 | 18 |
E2F (Fork head/winged helix factors) | 24 | 24 |
ELF/ELK (Tryptophan cluster factors) | 26 | 22 |
Zn–TF (C2H2 zinc finger factors and nuclear receptors with C4 zinc finger) | 140 | 72 |
TOTAL | 1014 | 764 |
δ-ALAD Activity | [MDA] | Ape1 Activity | APE1 mRNA | Ape1 Protein | |
---|---|---|---|---|---|
[PbB] | −0.72 *** | 0.60 *** | −0.43 *** | −0.53 *** | −0.24 ** |
δ-ALAD activity | −0.52 *** | 0.38 ** | 0.31 ** | NS | |
[MDA] | −0.33 ** | 0.31 ** | NS | ||
Ape1 activity | 0.37 ** | NS | |||
APE1 mRNA | NS |
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Hernández-Franco, P.; Maldonado-Vega, M.; Calderón-Salinas, J.V.; Rojas, E.; Valverde, M. Role of Ape1 in Impaired DNA Repair Capacity in Battery Recycling Plant Workers Exposed to Lead. Int. J. Environ. Res. Public Health 2022, 19, 7961. https://doi.org/10.3390/ijerph19137961
Hernández-Franco P, Maldonado-Vega M, Calderón-Salinas JV, Rojas E, Valverde M. Role of Ape1 in Impaired DNA Repair Capacity in Battery Recycling Plant Workers Exposed to Lead. International Journal of Environmental Research and Public Health. 2022; 19(13):7961. https://doi.org/10.3390/ijerph19137961
Chicago/Turabian StyleHernández-Franco, Pablo, María Maldonado-Vega, José Víctor Calderón-Salinas, Emilio Rojas, and Mahara Valverde. 2022. "Role of Ape1 in Impaired DNA Repair Capacity in Battery Recycling Plant Workers Exposed to Lead" International Journal of Environmental Research and Public Health 19, no. 13: 7961. https://doi.org/10.3390/ijerph19137961