In vivo and in vitro demonstration of reduced myelin synthesis following early postnatal exposure to ionizing radiation in the rat.

Irradiation of the immature central nervous system has been demonstrated histopathologically to result in a reduction in the quantity of myelin seen at later developmental ages [S. A. Gilmore, J. Neuropathol. Exp. Neurol. 22, 294-301 (1963). J. A. Beal and J. L. Hall, J. Neuropathol. Exp. Neurol. 33, 128-143 (1974)]. The results from our investigation indicate that this reduction in myelin content can be attributed to a decrease in sulfatide synthesis. Rats received whole-brain irradiation with 0, 500, 1500, 2000, or 2500 rad at 4 days postnatal (dpn). All of the rats exposed to 2000 or 2500 rad and 70% of those exposed to 1500 rad died within 6 to 10 days. At 17 dpn, animals received single intraperitoneal injections of [35S]sodium sulfate. Myelin synthesis, as indexed by the incorporation of sulfate into total lipids and glycolipids, was reduced in a dose-related fashion. To demonstrate a direct effect of ionizing radiation on myelinogenesis, brain cell reaggregate cultures derived from fetal rats were exposed at 12 days in vitro (div) to 0, 250, 500, 1000, or 1500 rad. A dose-related reduction in [35S]sulfate incorporation through 21 div was demonstrated. Reaggregates exposed to 250 or 500 rad but not 1000 or 1500 rad resumed normal myelin synthesis by 28 div. These changes occurred in the absence of histopathological changes, changes in protein content, and changes in the rate of protein synthesis.