02 May 2003 : Original article
Inhibition of poly (ADP-ribose) polymerase activity in vivo does not affect apoptosis induced by moderate g irradiation
L. Clarke, H. Louro, M. Silva, P. Costa, A. Ferro de Carvalho, M. BoavidaMed Sci Monit 2003; 9(1): 12- :: ID: 15059
Abstract
The aim of this study was to test the effectiveness of two potent PARP inhibitors in vivo, and to measure their effect on cellular apoptosis and DNA breakage following a low level genotoxic insult in C57Bl/6 mice. Animals were injected intraperitoneally with either PBS vehicle, 3-aminobenzamide (3-AB) or 5-aminoisoquinolinone (5-AIQ). Half of the animals were then subjected to 3 Gy whole body g-irradiation, and sacrificed three hours later. PARP activity was measured in spleen, and was found to be significantly stimulated following g-irradiation. Neither 3-AB nor 5-AIQ displayed significant inhibitory effects in the absence of the genotoxic insult, but both modulated the rise in PARP activity induced by radiation, significantly in the case of 3-AB. Apoptotic index (AI) was assessed in histological sections of spleen and colon by TUNEL assay, but although irradiation induced a significant multiple-fold increase of AI in both tissues after 3 hours, this was not affected by the inhibitory actions of 3-AB or 5-AIQ. Furthermore, neither inhibitor affected the induction of reticulocyte micronuclei, a measure of chromosomal damage, 48 h after treatment in irradiated or unirradiated mice. Our data suggest that inhibitors of PARP activity used in vivo do not abolish residual activity present in resting tissues, but can effectively stifle an excess of activity induced by DNA strand breakage. However, we also conclude that this excess has no measurable effect on the associated increase in cellular apoptosis and chromosomal breakage.
Keywords: PARP, 3-aminobenzamide, 5-aminoisoquinolinone, g-irradiation, micronuclei
397 0
Editorial
01 June 2023 : Editorial
Editorial: Infectious Disease Surveillance Using Artificial Intelligence (AI) and its Role in Epidemic and Pandemic PreparednessDOI: 10.12659/MSM.941209
Med Sci Monit 2023; 29:e941209
In Press
01 Jun 2023 : Clinical Research
Root Canal Numbers and Configurations in 1080 Permanent Canine Teeth in 270 Saudi Subjects Using Cone-Beam ...Med Sci Monit In Press; DOI: 10.12659/MSM.940472
01 Jun 2023 : Clinical Research
Internal Orifice Alloy Closure: A New Procedure for Treatment of Perianal Fistulizing Crohn’s DiseaseMed Sci Monit In Press; DOI: 10.12659/MSM.940873
01 Jun 2023 : Clinical Research
Effectiveness of Needle Aspiration versus Surgical Excision for Symptomatic Synovial Cysts of the Hip: A Si...Med Sci Monit In Press; DOI: 10.12659/MSM.940187
01 Jun 2023 : Clinical Research
Influence of Insulin Resistance on Diabetes NephropathyMed Sci Monit In Press; DOI: 10.12659/MSM.939482
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