Accelerated hematopoietic toxicity by high energy ⁵⁶Fe radiation

Abstract

Purpose: There is little information on the relative toxicity of highly charged (Z) high-energy (HZE) radiation in animal models compared to γ or X-rays, and the general assumption based on in vitro studies has been that acute toxicity is substantially greater.

Methods: C57BL/6J mice were irradiated with ⁵⁶Fe ions (1 GeV/nucleon), and acute (within 30 d) toxicity compared to that of γ rays or protons (1 GeV). To assess relative hematopoietic and gastrointestinal toxicity, the effects of ⁵⁶Fe ions were compared to γ rays using complete blood count (CBC), bone marrow granulocyte-macrophage colony forming unit (GM-CFU), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay for apoptosis in bone marrow, and intestinal crypt survival.

Results: Although onset was more rapid, ⁵⁶Fe ions were only slightly more toxic than γ rays or protons with lethal dose (LD)_50/30 (a radiation dose at which 50% lethality occurs at 30-day) values of 5.8, 7.25, and 6.8 Gy, respectively, with relative biologic effectiveness for ⁵⁶Fe ions of 1.25 and 1.06 for protons.

Conclusions: ⁵⁶Fe radiation caused accelerated and more severe hematopoietic toxicity. Early mortality correlated with more profound leukopenia and subsequent sepsis. Results indicate that there is selective enhanced toxicity to bone marrow progenitor cells, which are typically resistant to γ rays, and bone marrow stem cells, because intestinal crypt cells did not show increased HZE toxicity.

Keywords::

• Heavy ion radiation
• hematopoietic toxicity
• myeloid toxicity
• gastrointestinal toxicity
• space radiation

Acknowledgements

This work was supported by NASA Grants (NNX07AH70G and NNX09AU95G). Dr D. Trani was supported by the National Space Biomedical Research Institute (NSBRI) through NASA NCC9-58. Efforts at Memorial Sloan-Kettering Cancer Center were supported by National Cancer Institute (NCI) RO1-85704. We thank Dr K. Sree Kumar at Armed Forces Radiobiology Research Institute (AFRRI) for his valuable suggestions. We are also thankful to Dr Adam Rusek, Dr Peter Guida, and the NASA space radiation research laboratory at Brookhaven National Laboratory for their support.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.