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Title: Pharmacological Protection From Radiation {+-} Cisplatin-Induced Oral Mucositis

Abstract

Purpose: To evaluate if two pharmacological agents, Tempol and D-methionine (D-met), are able to prevent oral mucositis in mice after exposure to ionizing radiation {+-} cisplatin. Methods and Materials: Female C3H mice, {approx}8 weeks old, were irradiated with five fractionated doses {+-} cisplatin to induce oral mucositis (lingual ulcers). Just before irradiation and chemotherapy, mice were treated, either alone or in combination, with different doses of Tempol (by intraperitoneal [ip] injection or topically, as an oral gel) and D-met (by gavage). Thereafter, mice were sacrificed and tongues were harvested and stained with a solution of Toluidine Blue. Ulcer size and tongue epithelial thickness were measured. Results: Significant lingual ulcers resulted from 5 Multiplication-Sign 8 Gy radiation fractions, which were enhanced with cisplatin treatment. D-met provided stereospecific partial protection from lingual ulceration after radiation. Tempol, via both routes of administration, provided nearly complete protection from lingual ulceration. D-met plus a suboptimal ip dose of Tempol also provided complete protection. Conclusions: Two fairly simple pharmacological treatments were able to markedly reduce chemoradiation-induced oral mucositis in mice. This proof of concept study suggests that Tempol, alone or in combination with D-met, may be a useful and convenient way to prevent the severe oralmore » mucositis that results from head-and-neck cancer therapy.« less

Authors:
 [1];  [1];  [2]; ;  [1]; ; ; ;  [3];  [1]
  1. Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States)
  2. (Japan)
  3. Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States)
Publication Date:
OSTI Identifier:
22058980
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 83; Journal Issue: 4; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CHEMOTHERAPY; FEMALES; GELS; HEAD; INJECTION; IONIZING RADIATIONS; IRRADIATION; METHIONINE; MICE; NECK; NEOPLASMS; RADIATION DOSES; SAFETY; SIDE EFFECTS; TOLUIDINE BLUE; TONGUE; ULCERS

Citation Formats

Cotrim, Ana P., Yoshikawa, Masanobu, Department of Clinical Pharmacology, Tokai University School of Medicine, Kanagawa, Sunshine, Abraham N., Zheng Changyu, Sowers, Anastasia L., Thetford, Angela D., Cook, John A., Mitchell, James B., and Baum, Bruce J., E-mail: bbaum@dir.nidcr.nih.gov. Pharmacological Protection From Radiation {+-} Cisplatin-Induced Oral Mucositis. United States: N. p., 2012. Web. doi:10.1016/J.IJROBP.2011.09.026.
Cotrim, Ana P., Yoshikawa, Masanobu, Department of Clinical Pharmacology, Tokai University School of Medicine, Kanagawa, Sunshine, Abraham N., Zheng Changyu, Sowers, Anastasia L., Thetford, Angela D., Cook, John A., Mitchell, James B., & Baum, Bruce J., E-mail: bbaum@dir.nidcr.nih.gov. Pharmacological Protection From Radiation {+-} Cisplatin-Induced Oral Mucositis. United States. doi:10.1016/J.IJROBP.2011.09.026.
Cotrim, Ana P., Yoshikawa, Masanobu, Department of Clinical Pharmacology, Tokai University School of Medicine, Kanagawa, Sunshine, Abraham N., Zheng Changyu, Sowers, Anastasia L., Thetford, Angela D., Cook, John A., Mitchell, James B., and Baum, Bruce J., E-mail: bbaum@dir.nidcr.nih.gov. Sun . "Pharmacological Protection From Radiation {+-} Cisplatin-Induced Oral Mucositis". United States. doi:10.1016/J.IJROBP.2011.09.026.
@article{osti_22058980,
title = {Pharmacological Protection From Radiation {+-} Cisplatin-Induced Oral Mucositis},
author = {Cotrim, Ana P. and Yoshikawa, Masanobu and Department of Clinical Pharmacology, Tokai University School of Medicine, Kanagawa and Sunshine, Abraham N. and Zheng Changyu and Sowers, Anastasia L. and Thetford, Angela D. and Cook, John A. and Mitchell, James B. and Baum, Bruce J., E-mail: bbaum@dir.nidcr.nih.gov},
abstractNote = {Purpose: To evaluate if two pharmacological agents, Tempol and D-methionine (D-met), are able to prevent oral mucositis in mice after exposure to ionizing radiation {+-} cisplatin. Methods and Materials: Female C3H mice, {approx}8 weeks old, were irradiated with five fractionated doses {+-} cisplatin to induce oral mucositis (lingual ulcers). Just before irradiation and chemotherapy, mice were treated, either alone or in combination, with different doses of Tempol (by intraperitoneal [ip] injection or topically, as an oral gel) and D-met (by gavage). Thereafter, mice were sacrificed and tongues were harvested and stained with a solution of Toluidine Blue. Ulcer size and tongue epithelial thickness were measured. Results: Significant lingual ulcers resulted from 5 Multiplication-Sign 8 Gy radiation fractions, which were enhanced with cisplatin treatment. D-met provided stereospecific partial protection from lingual ulceration after radiation. Tempol, via both routes of administration, provided nearly complete protection from lingual ulceration. D-met plus a suboptimal ip dose of Tempol also provided complete protection. Conclusions: Two fairly simple pharmacological treatments were able to markedly reduce chemoradiation-induced oral mucositis in mice. This proof of concept study suggests that Tempol, alone or in combination with D-met, may be a useful and convenient way to prevent the severe oral mucositis that results from head-and-neck cancer therapy.},
doi = {10.1016/J.IJROBP.2011.09.026},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 4,
volume = 83,
place = {United States},
year = {Sun Jul 15 00:00:00 EDT 2012},
month = {Sun Jul 15 00:00:00 EDT 2012}
}