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

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.