Gallic acid provokes DNA damage and suppresses DNA repair gene expression in human prostate cancer PC-3 cells

2011 ◽  
Vol 28 (10) ◽  
pp. 579-587 ◽  
Author(s):  
Kuo-Ching Liu ◽  
Heng-Chien Ho ◽  
An-Cheng Huang ◽  
Bin-Chuan Ji ◽  
Hui-Yi Lin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Dna Damage ◽  
Dna Repair ◽  
Gallic Acid ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Repair Gene ◽  
Dna Repair Gene

scholarly journals Differential effects of silver nanoparticles on DNA damage and DNA repair gene expression in Ogg1-deficient and wild type mice

2017 ◽  
Vol 11 (8) ◽  
pp. 996-1011 ◽  
Author(s):  
Sameera Nallanthighal ◽  
Cadia Chan ◽  
Thomas M. Murray ◽  
Aaron P. Mosier ◽  
Nathaniel C. Cady ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Damage ◽  
Silver Nanoparticles ◽  
Dna Repair ◽  
Wild Type ◽  
Repair Gene ◽  
Differential Effects ◽  
Dna Repair Gene

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

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 842 ◽  
Author(s):  
Heng Wee Tan ◽  
Zhan-Ling Liang ◽  
Yue Yao ◽  
Dan-Dan Wu ◽  
Hai-Ying Mo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Damage ◽  
Dna Repair ◽  
Human Lung ◽  
Repair System ◽  
Dna Repair Genes ◽  
Repair Gene ◽  
Dna Repair Gene ◽  
Repair Genes ◽  
Cd Exposure

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.

scholarly journals Increased DNA Repair Gene Expression Correlates with MYC Expression and Inferior Progression-Free Survival in Multiple Myeloma Patients

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 48-49
Author(s):  
Karen Sweiss ◽  
Benjamin G Barwick ◽  
Gregory Sampang Calip ◽  
Damiano Rondelli ◽  
Craig C Hofmeister ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Damage ◽  
Dna Repair ◽  
High Risk ◽  
Research Funding ◽  
Excision Repair ◽  
Repair Gene ◽  
Dna Repair Gene ◽  
Whole Transcriptome Sequencing ◽  
Repair Pathways

High dose melphalan and autologous stem cell transplantation is standard of care for the upfront treatment of multiple myeloma (MM). Several studies have shown upregulation of single DNA repair genes and whole DNA repair pathways as associated with melphalan resistance and poor outcomes after ASCT. Here we set out to identify the most important DNA repair enzymes and pathways to predict outcomes after ASCT using the MMRF CoMMpass dataset but instead found DNA repair gene expression to be a poor prognostic feature regardless of treatment. Of the 561 MM patients who received ASCT as part of frontline therapy, 378 (67%) patients had whole transcriptome sequencing data available for analysis in this study. The majority of patients in this cohort received a 3-drug novel agent-based regimen for first line treatment. We selected 81 genes of known function related to DNA damage repair across multiple pathways. Using the median mRNA expression as cutoff for each gene, we first compared PFS for high vs. low expressers and found 38 genes in non-homologous end joining (NHEJ), homologous recombination (HR), nucleotide excision repair (NER), base excision repair (BER) and Fanconi anemia (FA) pathway which predicted for inferior survival with higher expression (p≤0.05). We subsequently analyzed each gene individually in a multivariate Cox proportional hazards models adjusted for known prognostic and treatment-related factors (age, gender, race, ISS stage, LDH, normal/abnormal cytogenetics, high risk FISH/cytogenetics, cycles to first response, frontline treatment, and time to transplant) and found that 9 genes retained significance including 3 genes in NHEJ (POLL, PRKDC, NHEJ1), 3 in FA pathway (BRIP1, RMI1, FANCE) and 3 in MMR (MLH3, MSH2 and PMS1). In addition, increased pathway level gene overexpression for NHEJ (p=0.02) and MMR (0.009) pathways conferred worse PFS. Genes involved in NER did not retain significance despite this pathway being involved with repair of melphalan-induced bulky adducts formation. Additionally, high MMR pathway expression was significant despite this pathway not having a known role in repair of melphalan-induced DNA damage. To validate the specific importance of these genes in predicting response to ASCT, we tested whether high expression predicted outcomes in patients who did not undergo ASCT. In 387 non-ASCT patients with whole transcriptome sequencing available, NHEJ and MMR gene expression were significant predictors of PFS confirming that this finding was not specific to patients undergoing ASCT. We next correlated the expression of NHEJ and MMR genes and found significant co-expression of these genes (r=0.55-0.8), suggesting a common mediator leading to global upregulation of DNA repair. As increased MYC activity is a common finding in MM and is a master regulator of transcription, we hypothesized the DNA damage repair genes were upregulated by increased MYC activity. Gene Set Enrichment Analysis of hallmark gene sets confirmed that patients with increased DNA repair were also enriched for MYC targets (FDR=0.0063). Based on this, we hypothesized that oncogene-mediated constitutive DNA damage and replication stress (RS) are a hallmark of high risk and aggressive myeloma. Here we present novel findings to show that global DNA repair upregulation occurs in high risk disease as evidenced by the inferior PFS. We hypothesize that this could be attributed to MYC-related increased gene transcription resulting in DNA damage and RS which in turn recruits several DNA repair pathways. These specific DNA repair pathways and signal activation pathways involved with replication stress represent novel therapeutic targets in myeloma. Disclosures Calip: Flatiron Health: Current Employment. Hofmeister:Sanofi: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Nektar: Honoraria, Research Funding; Imbrium: Honoraria; Janssen: Honoraria, Research Funding; Oncopeptides: Honoraria; Karyopharm: Honoraria, Research Funding; Oncolytics Biotech: Research Funding. Patel:Amgen: Consultancy; Celgene: Consultancy; Janssen: Consultancy.

scholarly journals DNA damage signalling barrier, oxidative stress and treatment-relevant DNA repair factor alterations during progression of human prostate cancer

2016 ◽  
Vol 10 (6) ◽  
pp. 879-894 ◽  
Author(s):  
Daniela Kurfurstova ◽  
Jirina Bartkova ◽  
Radek Vrtel ◽  
Alena Mickova ◽  
Alena Burdova ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Prostate Cancer ◽  
Dna Damage ◽  
Dna Repair ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Repair Factor ◽  
Dna Damage Signalling

Patients with Systemic Sclerosis Present Increased DNA Damage Differentially Associated with DNA Repair Gene Polymorphisms

2014 ◽  
Vol 41 (3) ◽  
pp. 458-465 ◽  
Author(s):  
Gustavo Martelli Palomino ◽  
Carmen L. Bassi ◽  
Isabela J. Wastowski ◽  
Danilo J. Xavier ◽  
Yara M. Lucisano-Valim ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Systemic Sclerosis ◽  
Blood Cells ◽  
Gene Polymorphisms ◽  
Peripheral Blood Cells ◽  
Dna Repair Genes ◽  
Repair Gene ◽  
Dna Repair Gene ◽  
Repair Genes

Objective.Patients with systemic sclerosis (SSc) exhibit increased toxicity when exposed to genotoxic agents. In our study, we evaluated DNA damage and polymorphic sites in 2 DNA repair genes (XRCC1Arg399Gln andXRCC4Ile401Thr) in patients with SSc.Methods.A total of 177 patients were studied for DNA repair gene polymorphisms. Fifty-six of them were also evaluated for DNA damage in peripheral blood cells using the comet assay.Results.Compared to controls, the patients as a whole or stratified into major clinical variants (limited or diffuse skin involvement), irrespective of the underlying treatment schedule, exhibited increased DNA damage.XRCC1(rs: 25487) andXRCC4(rs: 28360135) allele and genotype frequencies observed in patients with SSc were not significantly different from those observed in controls; however, theXRCC1Arg399Gln allele was associated with increased DNA damage only in healthy controls and theXRCC4Ile401Thr allele was associated with increased DNA damage in both patients and controls. Further, theXRCC1Arg399Gln allele was associated with the presence of antinuclear antibody and anticentromere antibody. No association was observed between these DNA repair gene polymorphic sites and clinical features of patients with SSc.Conclusion.These results corroborate the presence of genomic instability in SSc peripheral blood cells, as evaluated by increased DNA damage, and show that polymorphic sites of theXRCC1andXRCC4DNA repair genes may differentially influence DNA damage and the development of autoantibodies.

Regulation of DNA repair gene expression in human cancer cell lines

2006 ◽  
Vol 97 (5) ◽  
pp. 1121-1136 ◽  
Author(s):  
Claire J. McGurk ◽  
Michele Cummings ◽  
Beate Köberle ◽  
John A. Hartley ◽  
R. Timothy Oliver ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Repair ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Repair Gene ◽  
Human Cancer Cell Lines ◽  
Dna Repair Gene
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