Role of nerve growth factor in ethylnitrosourea-induced neural carcinogenesis.

Abstract

The sensitivity of the rat nervous system to malignant transformation by ethylnitrosourea (ENU) is a function of age at treatment. From late gestation, nervous structures decrease in sensitivity with age as non-neural structures increase in susceptibility. There is a decrease in the proportion of neural tumors induced by ENU and an increase in survival time when nerve growth factor (NGF) levels are elevated in the fetal or neonatal stage. If antibodies directed against mouse beta-NGF (anti-NGF) are administered prior to neonatal ENU treatment, neural tumors appear earlier, although in the same proportion as with treatment by ENU alone. This effect is not observed if the ENU is administered first. This phenomenon seems to be attributed to an increased number of trigeminal nerve neurinomas, which have a shorter latent period than other nervous system tumors. The induced neurological tumors in rats treated neonatally with anti-NGF prior to ENU seem to be almost exclusively neurinomas in the peripheral nervous system. Fetal anti-NGF treatment leads to an increased number of intracerebral gliomas and a longer survival time, which corresponds to the longer latent period of these tumors. The role of NGF in the sensitivity of the rat nervous system to carcinogenesis by ENU and its possible implications in the development of the nervous system discussed.