Early- and late-occurring damage in bone marrow cells of male CBA/Ca mice exposed whole-body to 1 GeV/n ⁴⁸Ti ions

Abstract

Purpose

To determine the early- and late-occurring damage in the bone marrow (BM) and peripheral blood cells of male CBA/Ca mice after exposure to 0, 0.1, 0.25, or 0.5 Gy of 1 GeV/n titanium (⁴⁸Ti) ions (one type of space radiation).

Method

We used the mouse in vivo blood-erythrocyte micronucleus (MN) assay for evaluating the cytogenetic effects of various doses of 1 GeV/n ⁴⁸Ti ions. The MN assay was coupled with the characterization of epigenetic alterations (the levels of global 5-methylcytosine and 5-hydroxymethylcytosine) in DNA samples isolated from BM cells. These analyses were performed in samples collected at an early time-point (1 week) and a late time-point (6 months) post-irradiation.

Results

Our results showed that ⁴⁸Ti ions induced genomic instability in exposed mice. Significant dose-dependent loss of global 5-hydroxymethylcytosine was found but there were no changes in global 5-methylcytosine levels.

Conclusion

Since persistent genomic instability and loss of global 5-hydroxymethylcytosine are linked to cancer, our findings suggest that exposure to ⁴⁸Ti ions may pose health risks.

Keywords:

• Bone marrow
• early- and late-occurring radiation-induced damage
• DNA methylation
• global 5-methylcytosine
• global 5-hydroxymethylcytosine

Acknowledgments

The authors thank Dr. Peter Guida and his team for logistic support, MaryAnn Petry and her staff at Brookhaven Laboratory Animal Facilities (BLAF) for their assistance in animal handling. The authors also thank Drs. Adam Rusek and Michael Sivertz for dosimetry support.

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This research was supported by the National Aeronautics and Space Administration (NASA) [Grant number NNX11AK91G].

Notes on contributors

Kanokporn Noy Rithidech

Kanokporn Noy Rithidech is a Professor in the Department of Pathology, Stony Brook University, Stony Brook, NY, USA. She is an experienced radiation biologist. One of the major efforts in her laboratory has been the identification of in vivo molecular biomarkers of response to and effects of radiation.

Witawat Jangiam

Witawat Jangiam is an Associate Professor at Burapha University, Thailand. He received his PhD in Biochemistry in 2008, and published articles in journals like International Journal of Radiation Biology and International Journal of Food Science. His main research interests include radiation biology and food science.

Montree Tungjai

Montree Tungjai is an Associated Professor at Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Thailand. His main research interest is radiation biology. 

Paiboon Reungpatthanaphong

Paiboon Reungpatthanaphong is the Chairman of Applied Radiation and Isotope Department, Kasetsart University, Bangkok, Thailand. Radition biology is one of his research interests. He has several publications relating to the biological effects of heavy ions found in the space environment.

Chris Gordon

Chris Gordon is an Excellent Research support specialist, with exceptional experience in cellular and molecular technologies. He has participated in all phases of the study.

Louise Honikel

Louise Honikel is a Senior Research support specialist. In addition to assisting Dr. Rithidech in all required technologies, she serves as a laboratory manager for Dr. Rithidech.