Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

02 May 2003

Investigating the role of poly(ADP-ribose) polymerase-1 in the response of human tumour cells to low doses of ionising radiation

A. Chalmers, M. Woodcock, P. Johnston

Med Sci Monit 2003; 9(1): 9-0 :: ID: 15055

Abstract

Background:The spectrum of DNA lesions induced by ionising radiation varies according to dose delivered; hence the relative importance of DNA repair proteins is also likely to vary with dose. Depletion or inhibition of PARP-1 is associated with radiosensitisation to doses of 2 Gy and above [1]; its activation by single strand breaks and interactions with the base excision repair pathway [2] suggest a potential role in the response to lower doses. Inhibition of PARP-1 may thus enhance the response of tumours to ultrafractionated and low dose rate radiotherapy protocols. We tested the effect of chemical inhibitors of PARP on low dose clonogenic survival in a range of hamster fibroblast and human tumour cell lines in PARP-1 knockout mouse embryo fibroblasts (MEF) [3]. Material/Methods: Clonogenic survival of T98G and U373 human glioma cells, V79 and CHO hamster fibroblasts, and 3T3 MEF PARP-1 knockout and control cells following low-dose irradiation in the presence of chemical PARP inhibitors was measured using a fluorescence-activated cell sorting assay [4].Results:Whilst PARP inhibition induced radiosensitisation of V79, CHO and T98G cells in the 0.05–0.5 Gy dose range, there was no such effect in the PARP-1 knockout cells compared with controls. Radiosensitisation to doses greater than 1.5 Gy occurred in all cell lines.Discussion:The discrepancy between the effect of chemical inhibition of PARP enzymes and deletion of the PARP-1 gene suggests that compensatory low dose repair mechanisms are upregulated in PARP-1 knockout cells, or that inhibition of both PARP-1 and PARP-2 is required for low dose radiosensitisation.References: 1.Shall S, de Murcia G: Mutation Research, 2000; 460: 1-15 2.Dantzer F, de la Rubia et al: Biochemistry, 2000; 39: 7559-69 3.de Murcia JM, Niedergang C et al: Proc Nat Acad Sci, 1997; 95: 7303-7 4.Skwarchuk MW, Wouters BG, Skarsgard LD: Int J Radiat Biol, 1993; 64: 601-12

Keywords: poly(ADP-ribose) polymerase-1, chemical inhibitors, low dose radiation

Add Comment 0 Comments

Editorial

01 June 2024 : Editorial  

Editorial: Concerns as Highly Pathogenic Avian Influenza (HPAI) Virus of the H5N1 Subtype is Identified in Dairy Cows and Other Mammals

Dinah V. Parums

DOI: 10.12659/MSM.945315

Med Sci Monit 2024; 30:e945315

0:00

In Press

Review article  

Applications of Functional Near-Infrared Spectroscopy (fNIRS) Neuroimaging During Rehabilitation Following ...

Med Sci Monit In Press; DOI: 10.12659/MSM.943785  

0:00

Clinical Research  

Epidemiology and Risk Factors for Revision Total Knee Arthroplasty in Chinese Patients: A Retrospective Stu...

Med Sci Monit In Press; DOI: 10.12659/MSM.943681  

Clinical Research  

Effects of the Cold Pressor Test on Popliteal Vein Diameter, Flow Velocity, and Blood Flow in the Lower Lim...

Med Sci Monit In Press; DOI: 10.12659/MSM.944560  

Clinical Research  

Outcomes of Anterior Lateral Approach and Gerdy's Tubercle Osteotomy for Tibial Plateau Fractures Involving...

Med Sci Monit In Press; DOI: 10.12659/MSM.943946  

Most Viewed Current Articles

14 Dec 2022 : Clinical Research   1,477,232

Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase Levels

DOI :10.12659/MSM.937990

Med Sci Monit 2022; 28:e937990

0:00

17 Jan 2024 : Review article   1,433,627

Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron Variant

DOI :10.12659/MSM.942799

Med Sci Monit 2024; 30:e942799

0:00

16 May 2023 : Clinical Research   690,157

Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...

DOI :10.12659/MSM.940387

Med Sci Monit 2023; 29:e940387

0:00

01 Jan 2022 : Editorial   50,150

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...

DOI :10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

0:00

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750