Hydrocephaly following fetal X irradiation.

Abstract

Ionizing radiation has its most profound effect on development during embryogenesis, particularly on the central nervous system. The neuroblast is the most radiosensitive element in the central nervous system and makes its appearance in the mouse embryo at seven days and in the human embryo on approximately the nineteenth gestation day. The most radiosensitive regions of the central nervous system change as the embryo grows and are probably related to the time lag for the appearance of these primitive neuroblast cells. Differentiation of the precursors takes place at various rates at the several sites. Thus, specific CNS anomalies depend on the age at which the embryo is exposed to x rays, rather than to the dose, although there is probably a threshold dose for each effect. Hicks (1) and Russell (2) have described a time table of malformations from experimental data on rats and have outlined a time scale comparing durations of pregnancy in mouse, rat, and man indicating the injuries produced by radiation at a given time in each species. Although conclusive data are lacking one can assume that selectively similar radiation damage to the central nervous system during identical stages of its development in the various animals is probable. Human data are difficult to evaluate because of lack of controls and deficient and often inaccurate dose data. Such extrapolations are precarious but nevertheless suggestive. One malformation encountered in human births is hydrocephalus. The etiology of this congenital anomaly has not been completely determined. Russell (3) believes that every case of hydrocephalus is due to some form of obstruction in the cerebrospinal fluid path. None of the cases she described was a result of x irradiation. Murphy (4) and Johnson (5) have reported single cases of hydrocephaly believed to be a result of therapeutic x irradiation. Because it is believed that some cases of human hydrocephalus may be due to radiation injury to the fetus, a study was designed to determine the doses and gestation ages showing statistically significant increments in radiation-induced hydrocephaly in the mouse. A technic for quantitatively assaying the degree of hydrocephalus is described, and the possible mechanisms for the development of hydrocephalus in mice are discussed.