Accelerated hematopoietic toxicity by high energy Fe-56 radiation

作者：Datta Kamal; Suman Shubhankar; Trani Daniela; Doiron Kathryn; Rotolo Jimmy A; Kallakury Bhaskar V S; Kolesnick Richard; Cole Michael F; Fornace Albert J Jr^*

来源：International Journal of Radiation Biology, 2012, 88(3): 213-222.

DOI：10.3109/09553002.2012.639434

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

Purpose: There is little information on the relative toxicity of highly charged (Z) high-energy (HZE) radiation in animal models compared to gamma 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 Fe-56 ions (1 GeV/nucleon), and acute (within 30 d) toxicity compared to that of gamma rays or protons (1 GeV). To assess relative hematopoietic and gastrointestinal toxicity, the effects of Fe-56 ions were compared to gamma 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, Fe-56 ions were only slightly more toxic than gamma 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 Fe-56 ions of 1.25 and 1.06 for protons. Conclusions: Fe-56 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 gamma rays, and bone marrow stem cells, because intestinal crypt cells did not show increased HZE toxicity.

• 出版日期2012-3