Abstract
Poly(ADP-ribose) glycohydrolase (Parg) is the main enzyme for degradation of poly(ADP-ribose) by splitting ribose-ribose bonds. Parg-deficient (Parg+/- and Parg-/-) mouse ES cell lines have been established by disrupting both alleles of Parg exon 1 through gene-targeting. A transcript encoding a full length isoform of Parg was eliminated and only low amounts of Parg isoforms were detected in Parg-/- embryonic stem (ES) cells. Poly(ADP-ribose) degradation activity was decreased to one-tenth of that in Parg+/+ ES cells. Parg-/- ES cells exhibited the same growth rate as Parg+/+ ES cells in culture. Sensitivity of Parg-/- ES cells to various DNA damaging agents, including an alkylating agent dimethyl sulfate, cisplatin, gemcitabine, 5-fluorouracil, camptothecin, and γ-irradiation was examined by clonogenic survival assay. Parg-/- ES cells showed enhanced lethality after treatment with dimethyl sulfate, cisplatin and γ-irradiation compared with wildtype (Parg+/+) ES cells (p < 0.05, respectively). In contrast, a sensitization effect by Parg-deficiency was not observed with gemcitabine and camptothecin. These results suggest the possibility that functional inhibition of Parg leads to sensitization of tumor cells to some chemo- and radiation therapies.
Keywords: Poly(ADP-ribose) glycohydrolase, Knockout, ES cell, DNA damaging agent, Alkylating agent, γ-irradiation, cisplatin, 5-fluorouracil
Current Cancer Drug Targets
Title: Poly(ADP-ribose) Glycohydrolase Deficiency Sensitizes Mouse ES Cells to DNA Damaging Agents
Volume: 9 Issue: 8
Author(s): H. Fujihara, H. Ogino, D. Maeda, H. Shirai, T. Nozaki, N. Kamada, K. Jishage, S. Tanuma, T. Takato, T. Ochiya, T. Sugimura and M. Masutani
Affiliation:
Keywords: Poly(ADP-ribose) glycohydrolase, Knockout, ES cell, DNA damaging agent, Alkylating agent, γ-irradiation, cisplatin, 5-fluorouracil
Abstract: Poly(ADP-ribose) glycohydrolase (Parg) is the main enzyme for degradation of poly(ADP-ribose) by splitting ribose-ribose bonds. Parg-deficient (Parg+/- and Parg-/-) mouse ES cell lines have been established by disrupting both alleles of Parg exon 1 through gene-targeting. A transcript encoding a full length isoform of Parg was eliminated and only low amounts of Parg isoforms were detected in Parg-/- embryonic stem (ES) cells. Poly(ADP-ribose) degradation activity was decreased to one-tenth of that in Parg+/+ ES cells. Parg-/- ES cells exhibited the same growth rate as Parg+/+ ES cells in culture. Sensitivity of Parg-/- ES cells to various DNA damaging agents, including an alkylating agent dimethyl sulfate, cisplatin, gemcitabine, 5-fluorouracil, camptothecin, and γ-irradiation was examined by clonogenic survival assay. Parg-/- ES cells showed enhanced lethality after treatment with dimethyl sulfate, cisplatin and γ-irradiation compared with wildtype (Parg+/+) ES cells (p < 0.05, respectively). In contrast, a sensitization effect by Parg-deficiency was not observed with gemcitabine and camptothecin. These results suggest the possibility that functional inhibition of Parg leads to sensitization of tumor cells to some chemo- and radiation therapies.
Export Options
About this article
Cite this article as:
Fujihara H., Ogino H., Maeda D., Shirai H., Nozaki T., Kamada N., Jishage K., Tanuma S., Takato T., Ochiya T., Sugimura T. and Masutani M., Poly(ADP-ribose) Glycohydrolase Deficiency Sensitizes Mouse ES Cells to DNA Damaging Agents, Current Cancer Drug Targets 2009; 9 (8) . https://dx.doi.org/10.2174/156800909790192419
DOI https://dx.doi.org/10.2174/156800909790192419 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Synthesis and Biological Evaluations of Organoruthenium Scaffolds: A Comprehensive Update
Current Organic Synthesis High-Level Secretory Expression and Purification of Recombinant Human Interleukin 1 Beta in Pichia pastoris
Protein & Peptide Letters Editorial [Hot topic: Contemporary Approaches in Cancer Therapy (Guest Editor: Riyaz Basha)]
Medicinal Chemistry Crocin Protects Against Beta-Amyloid Peptide-Induced Apoptosis in PC12 Cells Via the PI3 K Pathway
Current Molecular Pharmacology A Unique Intracellular, Extracellular and Transmembrane Circulation of Potassium Ions in the Auditory Inner Ear as an Anticarcinogenic Principle? Part 1
Inflammation & Allergy - Drug Targets (Discontinued) Bacterial Protein Toxins: Current and Potential Clinical Use
Current Medicinal Chemistry Non-Viral Gene Delivery to the Lungs
Current Gene Therapy Role of NF-κB and NF-κB-regulated Gene Products in Chemoresistance and Radioresistance
Current Cancer Therapy Reviews Modulation of Matrix Metalloproteinase Activity by Tobacco Cigarette Smoke
Current Chemical Biology Editorial [ Special Board Members Issue (Edior-in-Chief: Michelle Prudhomme)]
Anti-Cancer Agents in Medicinal Chemistry Editorial (Thematic Issue: Immunophilins, Protein Chemistry and Cell Biology of a Promising New Class of Drug Targets – Part II)
Current Molecular Pharmacology Design Strategies, Structures and Molecular Interactions of Small Molecule Src Inhibitors
Anti-Cancer Agents in Medicinal Chemistry ABC Transporters in Extrahepatic Tissues: Pharmacological Regulation in Heart and Intestine
Current Medicinal Chemistry Cutaneous Melanoma: Fishing with Chips
Current Molecular Medicine Gastrointestinal Stromal Tumors: A Paradigm for Therapeutic Options in Solid Organ Tumors
Mini-Reviews in Medicinal Chemistry Sanguinarine: A Double-Edged Sword of Anticancer and Carcinogenesis and Its Future Application Prospect
Anti-Cancer Agents in Medicinal Chemistry Modulating Mesenchymal Stromal Cell Function with Cholesterol Synthesis Inhibitors
Current Medicinal Chemistry Synthesis and Biological Activities of Organotin(IV) Complexes as Antitumoral and Antimicrobial Agents. A Review
Mini-Reviews in Medicinal Chemistry Multifunctional Nanoparticles, Nanocages and Degradable Polymers as a Potential Novel Generation of Non-Invasive Molecular and Cellular Imaging Systems
Recent Patents on Nanotechnology NF-κB Signaling Pathway Inhibitors as Anticancer Drug Candidates
Anti-Cancer Agents in Medicinal Chemistry