Hematological targets of radiation damage

Shilpa Kulkarni, Sanchita P. Ghosh, Martin Hauer-Jensen, K. Sree Kumar

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Radiation-induced myelosuppression remains a rate-limiting factor of radiotherapy and chemotherapy. Therefore, hematological targets of radiation damage are of great significance for radiation oncology and normal tissue injury and protection. Protection of hematopoietic stem and progenitor cells is pivotal. In order to develop therapeutic targets, it is necessary to understand the mechanisms of stem cell renewal and differentiation. Recent advances in the molecular pathology of hematopoietic stem cells indicate a fine balance between various extrinsic and intrinsic signaling pathways in preserving the self-renewal and proliferative capacity of stem cells. Extrinsic signaling involves microenvironment niche factors such as neighboring stromal cells, osteoblasts, and adipocytes secreting cytokines, chemokines, and metalloproteinases; intrinsic regulation involves Wnt/hedgehog/Notch signaling, DNA damage-induced epigenetic alterations, telomere shortening, and early senescence. Various drugs including synthetic cytokine mimetics, cytokine stimulators, and DNA repair modulators are being tested as radioprotectants. Colony-stimulating factors are routinely used in clinics to treat neutropenia induced by chemotherapy and radiotherapy as well as to mobilize and expand progenitors used in autologous transplantation. However, toxicity has limited their use. The vitamin E isoform gamma tocotrienol, a potent free radical scavenger that has displayed promising anticarcinogenic properties, was recently shown to protect bone marrow (BM) from radiation injury and to stimulate hematopoiesis in a murine model. This chapter focuses on the potential targets of radiation damage in BM and speculates on the mechanisms of protection by γ- tocotrienol and how these mechanisms can contribute to radioprotection in general and to protection of BM during chemotherapy and radiotherapy in particular.

Original languageEnglish (US)
Pages (from-to)1375-1385
Number of pages11
JournalCurrent Drug Targets
Volume11
Issue number11
StatePublished - 2010
Externally publishedYes

Fingerprint

Chemotherapy
Radiation damage
Radiotherapy
Hematopoietic Stem Cells
Stem cells
Bone
Bone Marrow
Radiation
Cytokines
Drug Therapy
Tocotrienols
Telomere Shortening
Colony-Stimulating Factors
Radiation Injuries
Free Radical Scavengers
Radiation Oncology
Oncology
Molecular Pathology
Autologous Transplantation
DNA

Keywords

  • Gamma tocotrienol
  • Hematopoietic stem cells
  • Pancytopenia
  • Radiation countermeasures

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Clinical Biochemistry
  • Molecular Medicine

Cite this

Kulkarni, S., Ghosh, S. P., Hauer-Jensen, M., & Kumar, K. S. (2010). Hematological targets of radiation damage. Current Drug Targets, 11(11), 1375-1385.

Hematological targets of radiation damage. / Kulkarni, Shilpa; Ghosh, Sanchita P.; Hauer-Jensen, Martin; Kumar, K. Sree.

In: Current Drug Targets, Vol. 11, No. 11, 2010, p. 1375-1385.

Research output: Contribution to journalArticle

Kulkarni, S, Ghosh, SP, Hauer-Jensen, M & Kumar, KS 2010, 'Hematological targets of radiation damage', Current Drug Targets, vol. 11, no. 11, pp. 1375-1385.
Kulkarni S, Ghosh SP, Hauer-Jensen M, Kumar KS. Hematological targets of radiation damage. Current Drug Targets. 2010;11(11):1375-1385.
Kulkarni, Shilpa ; Ghosh, Sanchita P. ; Hauer-Jensen, Martin ; Kumar, K. Sree. / Hematological targets of radiation damage. In: Current Drug Targets. 2010 ; Vol. 11, No. 11. pp. 1375-1385.
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