The aim of this study is to evaluate medium to low dose radiation injury to the developing fetal immune system with the ultimate goal of determining if this injury could be important in the pathogenesis of radiation-induced lymphoid neoplasia. The thymus gland is critical for normal development of immunological function and prenatal damage could lead to immunoregulatory or immunodeficiency disorders. Such disorders have been associated with an increased prevalence of lymphoid neoplasia. Preliminary studies demonstrated significant radiation-induced thymic epithelial cell injury after prenatal exposures. The proposed experiment will extend these observations by evaluating the persistence of prenatal thymic injury in postnatal life including functional immunologic abnormalities. The study is designed to develop dose-response relationships for prenatal immunologic injury and to determine whether effects can be demonstrated at low doses pertinent to current concerns over radiation carcinogenesis. A total of 120 beagle dog fetuses will be given 0, 10, 50, 100 or 150 rads whole-body 60Co gamma radiation at 35 days of gestation. Dogs in each dose group will be sacrificed and necropsied as 45 day fetuses, or 6-month-old puppies. Evaluation of the persistence, nature and degree of injury to thymus and other lymphoid tissues will be accomplished using qualitative histopathology and quantitative histomorphometry. Morphometry has proven to be a highly sensitive indicator of injury in this system and will be the primary method for elucidation of dose-response relationships. The postnatal immune system will be evaluated using state of the art procedures for immune function testing. Monoclonal antibodies will be used to enumerate changes in B and T lymphocyte populations in blood and tissues. Functional tests will include immunoglobulin quantitation and in vitro assays of B and T cell responses, including evaluation of the function of T-helper, T-cytoxic and T-suppressor cells, and macrophage function.
| Milisen, W B; Miller, G K; Benjamin, S A et al. (1988) The growth of nonlymphoid thymic components in vitro: age-related differences during development. In Vitro Cell Dev Biol 24:972-80 |
| Milisen, W B; Benjamin, S A; Miller, G K (1988) Effects of irradiation on the nonlymphoid thymus in vitro. Radiat Res 115:84-95 |
