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. JohnstonMed 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
231 0
Editorial
01 May 2023 : Editorial
Editorial: Twenty Years On from Sequencing the Human Genome, Personalized/Precision Oncology Prepares to Meet the Challenges of Checkpoint Inhibitor TherapyDOI: 10.12659/MSM.940911
Med Sci Monit 2023; 29:e940911
In Press
28 May 2023 : Database Analysis
Scientometric and Visualized Analysis of Intravoxel Incoherent Motion Magnetic Resonance Imaging: 1988-2021Med Sci Monit In Press; DOI: 10.12659/MSM.938715
25 May 2023 : Database Analysis
The COVID-19 Crisis and the Incidence of Alcohol-Related Deaths in PolandMed Sci Monit In Press; DOI: 10.12659/MSM.940904
25 May 2023 : Review article
A Review of Preclinical and Clinical Studies in Support of the Role of Non-Steroidal Anti-Inflammatory Drug...Med Sci Monit In Press; DOI: 10.12659/MSM.940635
25 May 2023 : Clinical Research
Periapical Lesions and Missed Canals in Endodontically Treated Teeth: A Cone-Beam Computed Tomographic Stud...Med Sci Monit In Press; DOI: 10.12659/MSM.940533
Most Viewed Current Articles
13 Nov 2021 : Clinical Research
Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...DOI :10.12659/MSM.932788
Med Sci Monit 2021; 27:e932788
30 Dec 2021 : Clinical Research
Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...DOI :10.12659/MSM.935379
Med Sci Monit 2021; 27:e935379
08 Mar 2022 : Review article
A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...DOI :10.12659/MSM.936292
Med Sci Monit 2022; 28:e936292
01 Jan 2022 : Editorial
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