The in vitro sensitivities to radiation and misonidazole of mouse bone marrow cells derived from different microenvironments.

Previous studies had indicated that haematopoietic cells (CFU-GM) which reside within compact bone are resistant to ionizing radiation and sensitive to the cytotoxic action of misonidazole (MISO) relative to cells which reside within the core of mouse femurs. It was postulated that the microenvironment within compact bone might be relatively hypoxic. CFU-GM from femur cores (Fraction 1) and from compact bone (Fraction 3) have been exposed to ionizing radiation and to the hypoxic cell radiosensitizer, MISO, under controlled conditions of oxygenation in vitro. The inherent radiosensitivity of aerated Fraction 1 CFU-GM is similar to their in vivo radiosensitivity. An oxygen enhancement ratio of 2.2 is observed for these cells in vitro. On the other hand, the in vitro radiosensitivity of hypoxic Fraction 3 CFU-GM was similar to their in vivo radiosensitivity. The oxygen enhancement ratio for Fraction 3 cells was 1.5, significantly lower than that observed for Fraction 1 cells. When CFU-GM cells were exposed to MISO under hypoxic conditions in vitro it was found that Fraction 3 CFU-GM were more sensitive to its cytotoxic action than were cells from Fraction 1. These data are consistent with the interpretation that some CFU-GM reside in an environment of relative hypoxia within the compact bone of the mouse femur.