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Clinical & Experimental Metastasis

, Volume 28, Issue 8, pp 803–810 | Cite as

High-dose ionizing radiation-induced hematotoxicity and metastasis in mice model

  • Jang Woo Shin
  • Jin Young Son
  • Hanumantha Rao Balaji Raghavendran
  • Weon Kyu Chung
  • Hyeong Geug Kim
  • Hye Jung Park
  • Seong Soon Jang
  • Chang Gue SonEmail author
Research Paper

Abstract

Radiotherapy induces untargeted effects on normal tissues such as bone marrow. So alteration of microenvironment by ionizing irradiation is supposed to influence dynamic host-cancer ecosystem affecting cancer behavior including metastasis. Herein, the incidence of lung metastasis after high-dose irradiation has been investigated using mice model having real-time condition of leucopenia. C57BL/6 mice were pre-exposed to a X-irradiation dose of 6 Gy on previous days 2, 5, 7, 10. Complete hematological parameters including lymphocyte subpopulation in blood and lung tissues were analyzed. Additionally, a group of mice including a non-irradiated group were inoculated with B16F10 cells (3 × 105/200 μl) via tail vein at the same day, and lung metastasized colonies were compared among groups at day 14 of post-inoculation. We observed that (i) total leucocytes and platelet were gradually depleted by day 10; (ii) lung tissue showed gradual infiltration of leucocytes including neutrophils and lymphocytes; (iii) pulmonary colonies were maximum and minimum on day 5 and 10 respectively; (iv) lymphocyte subpopulation analysis showed most number of natural killer (NK) cells in lung tissues on day 10; (v) gene expression of platelet/endothelial cell adhesion molecule (PECAM) in lung tissues peaked on day 5. To sum-up the study, severity of leucopenia did not influence the incidence of metastasis but blood platelets and microenvironment alteration of targeting tissue may be responsible factors for lung metastasis in our experimental model.

Keywords

Radiotherapy Hematotoxicity Lymphocyte subpopulation Metastasis Natural killer 

Notes

Acknowledgments

This study was supported by a grant from the National Research Foundation of Korea (R01-2007-000-11248-0) from the Ministry of Education, Science and Technology, Republic of Korea.

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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Jang Woo Shin
    • 1
  • Jin Young Son
    • 1
  • Hanumantha Rao Balaji Raghavendran
    • 1
  • Weon Kyu Chung
    • 2
  • Hyeong Geug Kim
    • 1
  • Hye Jung Park
    • 1
  • Seong Soon Jang
    • 3
  • Chang Gue Son
    • 1
    Email author
  1. 1.Liver and Immunology Research CenterDaejeon Oriental Hospital of Oriental Medical College of Daejeon UniversityDaejeonRepublic of Korea
  2. 2.Department of Radiation OncologyEast–West Neo Medical Center of Kyung Hee UniversitySeoulRepublic of Korea
  3. 3.Department of Radiation Oncology, Daejeon College of MedicineCatholic University of KoreaSeoulRepublic of Korea

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