Abstract
We previously reported that mice continuously irradiated with gamma-ray at low-dose-rate (LDR) of 21 mGy/day for 400 days showed higher incidence of leukemia than non-irradiated mice. However, little is known of the mechanisms underlying development of leukemia induced by LDR-irradiation. In this study, we compared cell differentiation stage of leukemias induced by gamma-rays at three different dose-rates. In mice irradiated at three different dose-rates of gamma rays [high dose rate (HDR): 1.0 Gy/min (total dose of 3 Gy), medium dose rate (MDR): 400 mGy/day (4 Gy) and LDR: 20 mGy/day (8Gy)] and non-irradiated mice, 10, 6, 3 and 10 leukemias were, respectively found. Hematopoietic cell-differentiation stages were analyzed by FACS in the bone marrow and spleen cells from the mice bearing leukemias. The analysis showed that significant increases of LSK- population with features of hematopoietic stem cell, lineage marker- (Lin-), Sca1+, c-kit+ and CD34- were found commonly in all groups of leukemia. However, leukemias from MDR and LDR-irradiated and non-irradiated mice showed increase of Lin- Sca1- c-kit+ CD34+ population, which is similar to common lymphoid progenitor, and their incidences were 80% (8/10 cases), 66% (2/3) and 66% (4/6), respectively. In contrast, HDR showed expansion of Lin- Sca1+ c-kit- CD34+ population resembling common myeloid progenitor and the incidence was 80% (8/10). Furthermore, when 100 cells at each different stage of cell populations of bone marrow cells from leukemic mice sorted by FACS were transplanted into a syngeneic mouse, CD45R/B220+ or Gr-1+ population in MDR, and LSK- or common myeloid progenitor-like population in HDR had an overt potential to develop leukemia in recipient mice. These findings indicate a possibility that differentiation stages and patterns of leukemic stem cell are influenced by dose-rates of gamma-rays. This study was performed under contract with the Aomori Prefectural Government, Japan.
