Histopathological studies of the nervous system tumors in rats induced by transplacental administration of ethylnitrosourea (Japanese)

Abstract

Rats were given a single dose of 50 mg/kg of N ethyl N nitrosourea (ENU) dissolved in 0.5 ml sterile saline on the 15th day (Group I, 9 rats) and the 20th day (Group II, 7 rats) of gestation. A total of 126 tumors (Group I, 61 and Group II, 65) were produced in 92 (Group I, 46 and Group II, 46) of the 117 treated offspring which had survived into tumor bearing age. The mean survival time of Group I animals with tumor development was 317 days after birth and that of Group II animals was 276. Of a total of 126 tumors, 27 were produced in the brain (Group I, 21 and Group II, 6), 21 in the spinal cord, 42 in the cranial nerves and ganglia, 8 in the spinal nerve roots, 6 in the peripheral nerves and 22 in the extraneural organs. The neural tumors totalled 104, comprising 82.5% of the total number of the neoplasms. Almost all the cranial nerve tumors were found arising from the trigeminal nerve and Gasserian ganglia. Significant differences in incidence of the tumors of the brain and those in extraneural organs were demonstrated between Group I and Group II animals. According to the cytology and pattern of predominant tumor cells, tumors of the brain and spinal cord were classified into 5 types; mixed glioma, oligodendroglioma, anaplastic astrocytoma or anaplastic glioma, ependymoma like tumor and unclassified tumor. Among various histological types of gliomas, those with the histology of mixed glioma and oligodendroglioma were most common. Some of the mixed gliomas showed an irregular admixture of astroglial and oligodendroglial components. Others were composed of more than 2 areas of different histology. Five tumors produced in the spinal cord were classified as ependymoma like. They showed an isomorphic cell appearance with such architectural characteristics as crowns of cell nuclei around vascular vessels and pseudorosettes. No tumors were found with typical ependymal rosettes. Indirect fluorescent antibody technique using anti S 100 protein RGG and fluorescein labeled antirabbit globulin was applied to some tumors produced in the brain. A strong affinity of the stain was demonstrated to the cytoplasm of occasional neoplastic cells. Besides grossly visible tumors, histological examinations of the brain and spinal cord disclosed a total of 138 (Group I, 84 and Group II, 54) foci of glial cell hyperplasia or tumors of microscopic size. Sites of predilection for such foci or small microtumors were the subcortical white matter of the brain, the hippocampus, the periventricular areas, the basal ganglia and the spinal cord. The predominant cell type of such lesions was either oligodendroglial or astrocytic. With increasing tumor size, a number of microtumors with a mixed cellular composition became frequent. A total of 56 tumors of the peripheral nervous system were produced in this experiment, in which those of the cranial nerves comprised 75% of the total. Microscopically, the majority of neurinomas were highly anaplastic often with frequent mitotic figures. The transplantation experiment demonstrated that anaplastic neurinomas were highly transplantable and capable of subsequent transfers through a number of generations.