Tocols induce G-CSF and mobilise progenitors that mitigate radiation injury

• Published in: Radiation protection dosimetry 2014-11, Vol.162 (1-2), p.83-87
• Main Authors: Singh, Vijay K, Romaine, Patricia L P, Newman, Victoria L, Seed, Thomas M
• Format: Article
• Language: English
• Subjects: Animals; Anti-HIV Agents - pharmacology; Gamma Rays - adverse effects; Granulocyte Colony-Stimulating Factor - metabolism; Hematopoietic Stem Cell Mobilization; Heterocyclic Compounds - pharmacology; Leukocytes, Mononuclear - transplantation; Male; Mice; Radiation Injuries - etiology; Radiation Injuries - prevention & control; Radiation-Protective Agents - pharmacology; Tocopherols - pharmacology
• ISSN: 0144-8420; 1742-3406
• DOI: 10.1093/rpd/ncu223

Tocols induce high levels of granulocyte-colony-stimulating factor (G-CSF). G-CSF mobilises progenitors that allow mice that have been severely immunocompromised by exposure to acute, high-dose ionising irradiation to recover and to survive. The neutralisation of G-CSF abrogates the radioprotective efficacy of tocols. This article reviews studies in which CD2F1 mice were irradiated with sufficiently high doses to cause acute radiation syndrome symptoms and then administered (iv) progenitor-enriched whole blood or peripheral blood mononuclear cells from tocol- and AMD3100-injected donor mice (AMD3100 is a chemokine receptor antagonist used to improve the yield of mobilised progenitors). In some experiments, G-CSF was neutralised completely. Irradiated recipient mice were observed for 30 d post-irradiation for survival, a primary endpoint used for determining therapeutic effectiveness. Additionally, potential tocol-induced biomarkers (cytokines, chemokines and growth factors) were quantified. The authors suggest that tocols are highly effective agents for mobilising progenitors with significant therapeutic potential.