High Radiosensitivity of the Mineralization Capacity of Adult Murine Bone Marrow in Vitro to Continuous α-irradiation Compared to Acute X-irradiation

Abstract

Adult BALB/c mice, injected with osteosarcomogenic amounts of ²⁴¹Am (between 40 and 500 Bq/g mouse) showed an impaired mineralization capacity of their femoral bone marrow. This effect persisted until at least 1 year after ²⁴¹Am injection and was expressed after incubation of bone marrow cells in vitro in conditions allwoing osteogenic differentiation. The mineralization capacity of marrow in vitro was evaluated by measurement of ⁸⁵Sr uptake from the tissue culture medium. Two osteogenic assays were used: in marrow cultured as an intact organ (marrow organ cultures), reduced mineralization was observed in mice given 149 Bq ²⁴¹Am/g mouse or more (skeletal dose rate of 25 mGy/day), in stromal marrow cells cultured from adherent cell layers and subsequently brought into a three-dimensional (3D) mineralizing condition (stromal 3D cultures), reduced ⁸⁵Sr uptake was observed from the lowest dose level tested (42 Bq ²⁴¹Am/g mouse, skeletal dose rate of 7 mGy/day). Taking into account that only a fraction of the skeletal α-dose reached the marrow of the femoral diaphyses, marrow organ cultures and stromal 3D cultures exhibited high radiosensitivity to α-irradiation in vivo. However, after acute X-irradiation of marrow in vivo or in vitro prior to initiation of the marrow organ cultures, X-ray doses of 4 Gy or higher were needed to significantly impair the mineralization capacity of marrow organ cultures in vitro. Our data demonstrated that the osteogenic cells from the bone marrow are subjected to long-term damage after low doses of continuous α-irradiation in vivo.