Genetic background and lymphocyte populations after total-body exposure to iron ion radiation

Abstract

Purpose: Particle radiations could significantly impact astronaut health during space missions. This study quantified the effects of iron ion radiation on lymphocytes in two strains of mice differing in susceptibility to radiation-induced acute myeloid leukemia (AML) and thymic lymphoma (TL): C57BL/6 (AML resistant, TL sensitive) and CBA/Ca (AML sensitive, TL resistant).

Materials and methods: The animals (n = 60/strain) were irradiated with ⁵⁶Fe²⁶⁺ (1 GeV) to total doses of 0, 0.5, 2 and 3 Gray (Gy) at an average dose rate of 1 Gy/min and euthanised on days 4 and 30 thereafter; blood, spleen, and bone marrow were collected for flow cytometry analyses. Cells expressing the following molecules were quantified: Cluster of differentiation (CD) 4, CD8, CD25, CD34, CD71, B220 (isoform of CD45 on B cells), NK1.1 (marker on natural killer or NK cells, C57B mice), panNK (marker on NK cells, CBA mice), and Sca1 (stem cell antigen 1).

Results: Exposure to radiation resulted in different distribution patterns in lymphocyte populations and leukocytes expressing activation and progenitor markers in the two mouse strains. Significant main effects were dependent upon strain, as well as radiation dose, body compartment, and time of assessment. Especially striking differences were noted on day 4 after 3 Gy irradiation, including in the CD4:CD8 ratio [blood, C57 (2.83 ± 0.25) vs. CBA (6.19 ± 0.24); spleen, C57 (2.29 ± 0.12) vs. CBA (4.98 ± 0.22)], %CD25⁺ mononuclear cells in bone marrow [C57 (5.62 ± 1.19) vs. CBA (12.45 ± 0.93)] and %CD34⁺Sca1⁺ cells in bone marrow [CD45^l° gate, C57 (2.72 ± 0.74) vs. CBA (21.44 ± 0.73)].

Conclusion: The results show that genetic background, as well as radiation dose and time post-exposure, had a profound impact on lymphocyte populations, as well as other leukocytes, after exposure to iron ion radiation.

Keywords:

• heavy particle radiation
• high-LET radiation
• T cells
• radiosensitivity
• mouse strain
• activation markers
• progenitor cells

Acknowledgements

The expert assistance of Gregory A. Nelson, PhD, Radha Dutta-Roy, Anna L. Smith, Tamako A. Jones, Melba L. Andres, Glen M. Miller, Dong Won Kim, Judy Folz-Holbeck, Lora Benzatyan, Mauricio DosSantos, and Maritess G. Asumen is greatly appreciated. Furthermore, the support of Marcelo Vazquez, MD, PhD, Mary Ann Kershaw, Katheryn Conkling, the AGS support staff at BNL, and the physics group from the Lawrence Berkeley Laboratory was essential. This study was supported by NASA grant no. NCC9-79 and the Department of Radiation Medicine of the LLU Medical Center.

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