Our laboratory has studied the embryotoxic effects of X-irradiation during many peroids of gestation and we have extensive data correlating morphologic and toxicologic effects with radiation dose. Since X-irradiation can alter cell proliferation, change the length of the mitotic cycle, produce cell death, and produce cytogenetic alterations, we will compare the dose relationships of the cytogenetic and cytokinetic effects of X-irradiation with the morphologic effects produced by X-irradiation. We will also examine the dose relationships of the cytokinetic effects to determine whether normal development after exposures which result in no permanent morphologic effects is due to a lack of significant cytokinetic effects or due to repair. We have focused on four specific aims in this proposal: 1) to study embryos on the 5th through the 8th day of gestation after irradiation on the first day in an attempt to explain the """"""""all-or-none"""""""" phenomenon; 2) to study the radiosensitivity of the inner cell mass stage (late morula through early blastocyst) to the production of cytogenetically abnormal embryos; 3) to study radiation induced changes in neural tissue cytokinetics in embryos exposed to various doses of X-rays during organogenesis; and 4) to study radiation induced neuroanatomic and cytokinetic alterations in the fetal rat brain irradiated during histogenetic stages in order to correlate these alterations with histologic changes in the rat brain at 30 days after birth. These studies will enable us to determine whether X-ray exposures which no longer produce anatomical malformations also no longer result in measurable changes in the cytokinetics of the developing embryo or whether cytokinetic alterations are produced but the embryo has the capacity to recover from these effects. This information will assist us in determining whether our present view of the levels of radiation which present a substantial risk to the developing embryo is appropriate or should be altered.
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