Modification of murine adult haemopoiesis and response to methyl nitrosourea following exposure to radiation at different developmental stages.

Abstract

PURPOSE: To investigate the hypothesis that the developmental phase at which an individual encounters radiation damage affects its long-term sensitivity to a subsequent tumourigenic insult. MATERIALS AND METHODS: Either the pregnant C57B16 mouse was exposed to 137Cs gamma-rays at 4 or 15 days post-conception (embryonic and foetal stages respectively) or BDF1 offspring were irradiated at 4 or 21 days of age (neonatal and juvenile stages). Offspring were either assayed for changes in bone marrow stem cells and committed progenitors at 6, 12 and 18 weeks of age, or injected with the chemical carcinogen methyl nitrosourea (MNU) at 10 weeks of age and monitored for onset of neoplasia. RESULTS: Gamma-irradiation induced a persistent long-term deficit in stem cells in all irradiated animals, with the foetal stage appearing most radiosensitive. However, femoral cellularity, committed progenitor cell numbers and peripheral blood counts were unaffected. When offspring were exposed to MNU, the incidence of malignancy was significantly enhanced in animals irradiated at the foetal, neonatal and juvenile stages. CONCLUSIONS: This study has shown that exposure to ionizing radiation at the foetal, neonate or juvenile stages of development induces residual haemopoietic damage and increases oncogenic susceptibility to a subsequent exposure to MNU.