Gamma-tocotrienol protects hematopoietic stem and progenitor cells in mice after total-body irradiation

Shilpa Kulkarni, Sanchita P. Ghosh, Merriline Satyamitra, Steven Mog, Kevin Hieber, Lyudmila Romanyukha, Kristen Gambles, Raymond Toles, Tzu Cheg Kao, Martin Hauer-Jensen, K. Sree Kumar

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

We analyzed the radioprotective effects of gamma-tocotrienol (GT3) on hematopoietic stem cells (HSCs) and progenitor cells (HPCs) in sublethally irradiated mice. Flow cytometry analysis indicated that radiation depleted HPCs (c-Kit+, Lin-) to 40 at days 2 and 4 after total-body irradiation (TBI) in all treatment groups. The HPC numbers in GT3-treated mice recovered almost completely (90) at day 7 but remained depleted in vehicle-treated mice (30) even at day 13 after TBI. An in vitro colony-forming assay on sorted HSCs (Lin-, Sca1+, c-Kit+) indicated that TBI reduced the number of colonies to 40 and 50 at day 17 and 60, respectively, in vehicle-treated groups compared to unirradiated controls (nave). GT3-treated irradiated mice maintained higher numbers of colonies (86 and 80 compared to nave mice), thereby preserving the self-renewable capacity of HSCs. Histopathology of sternal bone marrow indicated more regenerative microfoci for myeloid cells and megakaryocytes and higher overall cellularity in GT3-treated mice compared to vehicle controls at days 7 and 13 after TBI. GT3 treatment also reduced the frequency of micronucleated erythrocytes significantly in irradiated mice. Our results demonstrate that GT3 protected hematopoietic tissue by preserving the HSCs and HPCs and by preventing persistent DNA damage.

Original languageEnglish (US)
Pages (from-to)738-747
Number of pages10
JournalRadiation Research
Volume173
Issue number6
DOIs
StatePublished - Jun 1 2010

ASJC Scopus subject areas

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

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    Kulkarni, S., Ghosh, S. P., Satyamitra, M., Mog, S., Hieber, K., Romanyukha, L., Gambles, K., Toles, R., Kao, T. C., Hauer-Jensen, M., & Kumar, K. S. (2010). Gamma-tocotrienol protects hematopoietic stem and progenitor cells in mice after total-body irradiation. Radiation Research, 173(6), 738-747. https://doi.org/10.1667/RR1824.1