Amifostine Induces Antioxidant Enzymatic Activities in Normal Tissues and a Transplantable Tumor That Can Affect Radiation Response

David J Grdina; Jeffrey S Murley; Yasushi Kataoka; Kenneth L Baker; Rangesh Kunnavakkam; Mitchell C Coleman; Douglas R Spitz

doi:10.1016/j.ijrobp.2008.10.061

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Amifostine Induces Antioxidant Enzymatic Activities in Normal Tissues and a Transplantable Tumor That Can Affect Radiation Response

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Amifostine Induces Antioxidant Enzymatic Activities in Normal Tissues and a Transplantable Tumor That Can Affect Radiation Response

David J Grdina, Jeffrey S Murley, Yasushi Kataoka, Kenneth L Baker, Rangesh Kunnavakkam, Mitchell C Coleman and Douglas R Spitz

International journal of radiation oncology, biology, physics, Vol.73(3), pp.886-896

2009

DOI: 10.1016/j.ijrobp.2008.10.061

PMID: 19215822

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http://doi.org/10.1016/j.ijrobp.2008.10.061View

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Abstract

To determine whether amifostine can induce elevated manganese superoxide dismutase (SOD2) in murine tissues and a transplantable SA-NH tumor, resulting in a delayed tumor cell radioprotective effect. SA-NH tumor-bearing C3H mice were treated with a single 400 mg/kg or three daily 50 mg/kg doses of amifostine administered intraperitoneally. At selected time intervals after the last injection, the heart, liver, lung, pancreas, small intestine, spleen, and SA-NH tumor were removed and analyzed for SOD2, catalase, and glutathione peroxidase (GPx) enzymatic activity. The effect of elevated SOD2 enzymatic activity on the radiation response of SA-NH cells was determined. SOD2 activity was significantly elevated in selected tissues and a tumor 24 h after amifostine treatment. Catalase and GPx activities remained unchanged except for significant elevations in the spleen. GPx was also elevated in the pancreas. SA-NH tumor cells exhibited a twofold elevation in SOD2 activity and a 27% elevation in radiation resistance. Amifostine administered in three daily fractions of 50 mg/kg each also resulted in significant elevations of these antioxidant enzymes. Amifostine can induce a delayed radioprotective effect that correlates with elevated levels of SOD2 activity in SA-NH tumor. If limited to normal tissues, this delayed radioprotective effect offers an additional potential for overall radiation protection. However, amifostine-induced elevation of SOD2 activity in tumors could have an unanticipated deleterious effect on tumor responses to fractionated radiation therapy, given that the radioprotector is administered daily just before each 2-Gy fractionated dose.

Glutathione peroxidase

Tumor

Catalase

Amifostine

Manganese superoxide dismutase

Details

Title: Subtitle: Amifostine Induces Antioxidant Enzymatic Activities in Normal Tissues and a Transplantable Tumor That Can Affect Radiation Response
Creators: David J Grdina - Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL
Jeffrey S Murley - Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL
Yasushi Kataoka - Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL
Kenneth L Baker - Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL
Rangesh Kunnavakkam - Department of Health Studies, The University of Chicago, Chicago, IL
Mitchell C Coleman - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA
Douglas R Spitz - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA
Resource Type: Journal article
Publication Details: International journal of radiation oncology, biology, physics, Vol.73(3), pp.886-896
DOI: 10.1016/j.ijrobp.2008.10.061
PMID: 19215822
NLM abbreviation: Int J Radiat Oncol Biol Phys
ISSN: 0360-3016
eISSN: 1879-355X
Publisher: Elsevier Inc
Language: English
Date published: 2009
Academic Unit: Pathology; Orthopedics and Rehabilitation; Radiation Oncology
Record Identifier: 9984040263602771

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