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Media type:
E-Article
Title:
Amelioration of Radiation-Induced Pulmonary Fibrosis by a Water-Soluble Bifunctional Sulfoxide Radiation Mitigator (MMS350)
Contributor:
Kalash, Ronny;
Epperly, Michael W.;
Goff, Julie;
Dixon, Tracy;
Sprachman, Melissa M.;
Zhang, Xichen;
Shields, Donna;
Cao, Shaonan;
Franicola, Darcy;
Wipf, Peter;
Berhane, Hebist;
Wang, Hong;
Au, Jeremiah;
Greenberger, Joel S.
imprint:
Radiation Research Society, 2013
Published in:Radiation Research
Language:
English
ISSN:
0033-7587;
1938-5404
Origination:
Footnote:
Description:
<p>A water-soluble ionizing radiation mitigator would have considerable advantages for the management of acute and chronic effects of ionizing radiation. We report that a novel oxetanyl sulfoxide (MMS350) is effective both as a protector and a mitigator of clonal mouse bone marrow stromal cell lines in vitro, and is an effective in vivo mitigator when administered 24 h after 9.5 Gy (LD100/30) total-body irradiation of C57BL/6NHsd mice, significantly improving survival (P = 0.0097). Furthermore, MMS350 (400 μM) added weekly to drinking water after 20 Gy thoracic irradiation significantly decreased: expression of pulmonary inflammatory and profibrotic gene transcripts and proteins; migration into the lungs of bone marrow origin luciferase+/GFP+ (luc+/GFP+) fibroblast progenitors (in both luc+ marrow chimeric and luc+ stromal cell line injected mouse models) and decreased radiation-induced pulmonary fibrosis (P < 0.0001). This nontoxic and orally administered small molecule may be an effective therapeutic in clinical radiotherapy and as a counter measure against the acute and chronic effects of ionizing radiation.</p>