WR-1065, the active metabolite of amifostine, mitigates radiation-induced delayed genomic instability

Jaroslaw Dziegielewski; Janet E Baulch; Wilfried Goetz; Mitchell C Coleman; Douglas R Spitz; Jeffrey S Murley; David J Grdina; William F Morgan

doi:10.1016/j.freeradbiomed.2008.09.004

Back

WR-1065, the active metabolite of amifostine, mitigates radiation-induced delayed genomic instability

Journal article

Peer reviewed

WR-1065, the active metabolite of amifostine, mitigates radiation-induced delayed genomic instability

Jaroslaw Dziegielewski, Janet E Baulch, Wilfried Goetz, Mitchell C Coleman, Douglas R Spitz, Jeffrey S Murley, David J Grdina and William F Morgan

Free radical biology & medicine, Vol.45(12), pp.1674-1681

2008

DOI: 10.1016/j.freeradbiomed.2008.09.004

PMCID: PMC2629584

PMID: 18845240

View Online

Abstract

Compounds that can protect cells from the effects of radiation are important for clinical use, in the event of an accidental or terrorist-generated radiation event, and for astronauts traveling in space. One of the major concerns regarding the use of radio-protective agents is that they may protect cells initially, but predispose surviving cells to increased genomic instability later. In this study we used WR-1065, the active metabolite of amifostine, to determine how protection from direct effects of high- and low-LET radiation exposure influences genomic stability. When added 30 min before irradiation and in high concentrations, WR-1065 protected cells from immediate radiation-induced effects as well as from delayed genomic instability. Lower, nontoxic concentrations of WR-1065 did not protect cells from death; however, it was effective in significantly decreasing delayed genomic instability in the progeny of irradiated cells. The observed increase in manganese superoxide dismutase protein levels and activity may provide an explanation for this effect. These results confirm that WR-1065 is protective against both low- and high-LET radiation-induced genomic instability in surviving cells.

High-LET radiation

Radio-protection

WR-1065

Amifostine

Delayed effects

Genomic instability

Details

Title: Subtitle: WR-1065, the active metabolite of amifostine, mitigates radiation-induced delayed genomic instability
Creators: Jaroslaw Dziegielewski - Department of Radiation Oncology, Radiation Oncology Research Laboratory, University of Maryland School of Medicine, Baltimore, MD, USA
Janet E Baulch - Department of Radiation Oncology, Radiation Oncology Research Laboratory, University of Maryland School of Medicine, Baltimore, MD, USA
Wilfried Goetz - Department of Radiation Oncology, Radiation Oncology Research Laboratory, University of Maryland School of Medicine, Baltimore, MD, USA
Mitchell C Coleman - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA
Douglas R Spitz - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA
Jeffrey S Murley - Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, USA
David J Grdina - Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, USA
William F Morgan - Department of Radiation Oncology, Radiation Oncology Research Laboratory, University of Maryland School of Medicine, Baltimore, MD, USA
Resource Type: Journal article
Publication Details: Free radical biology & medicine, Vol.45(12), pp.1674-1681
DOI: 10.1016/j.freeradbiomed.2008.09.004
PMID: 18845240
PMCID: PMC2629584
NLM abbreviation: Free Radic Biol Med
ISSN: 0891-5849
eISSN: 1873-4596
Publisher: Elsevier Inc
Language: English
Date published: 2008
Academic Unit: Pathology; Orthopedics and Rehabilitation; Radiation Oncology
Record Identifier: 9984040293402771

Metrics

21 Record Views

38 Times Cited - Web of Science

See more details