Administration of
nerve growth factor (
NGF) to the offspring of Sprague-Dawley rats transplacentally exposed to 50 mg/kg
ethylnitrosourea on the 20th day of gestation resulted in a significant reduction of trigeminal and peripheral nerve
neurinomas. Forty, 60, and 80 micrograms of
NGF was administered in five s.c. doses, one dose on each of days 12-16, 90-94, and 210-214 postnatally. Of the 34 rats in the
NGF-treated group, 11 animals were affected with trigeminal nerve
neurinomas as compared to 18/34 in the
NGF-untreated group (P less than 0.05). In the peripheral nerves (spinal cord nerve roots) there were five and 11
neurinomas, respectively, in each group of 34 rats. When the total numbers of
neurinomas (trigeminal and peripheral nerves) between these groups were compared (16/34 versus 29/34), the significance of
neurinoma reduction was P less than 0.01. Five trigeminal and two peripheral
neurinomas in the
NGF-untreated group were shown by immunohistochemical staining to contain
nerve growth factor receptor protein, whereas none of the
neurinomas in the
NGF-treated group were positive for the receptor
protein. The results obtained from this experiment lend support to the hypothesis that
NGF has the capability to reduce the oncogenic consequences of
ethylnitrosourea exposure perhaps by the process of maturation and/or differentiation of the transformed cells, and that this effect may depend upon the presence of receptor binding sites.