Induction of neurogenic tumors in C3HeB/FeJ mice by nitrosourea derivatives: Observations by light microscopy, tissue culture, and electron microscopy

Neurogenic tumors were induced in 32.3% of C3HeB/FeJ mice treated transplacentally with ethylnitrosourea (ENU) and in 10.5% of mice treated intravenously (IV) with methylnitrosourea (MNU). Earlier reports on other strains of mice treated with nitrosourea derivatives indicated that non‐neural tumors, particularly lymphomas, were readily induced. However, tumors of the nervous system did not develop or occurred only in a low percentage of treated mice. Genetic strain of mice appears to influence susceptibility of mice to nitrosoureas. Two brain tumors, an oligodendroglioma in the diencephalon and a mixed neuroblastoma‐glioma of the cerebellum, occurred in 19 adult male mice treated IV every 4 weeks with 25 mg/kg MNU to a total of 175 mg/kg. Neurinomas of cranial nerves developed in 9 of 31 offspring of pregnant mice treated with 20 mg/kg ENU IV on the 19th day of gestation. One MNU‐induced oligodendroglioma and 1 ENU‐induced neurinoma were propagated in tissue culture. Cells of both tumors produced intracerebral (IC) and subcutaneous (SC) tumors following injection into syngeneic mice. Tissue samples from both IC transplanted tumors contained abundant clusters of C‐type RNA viruses in interstitial spaces. Budding virus particles were readily demonstrated on the plasma membranes of tumor cells.