gp130RB13-6-positive neural progenitor cells are susceptible to the oncogenic effect of ethylnitrosourea in pre-natal rat brain.

Proliferation-competent rat brain precursor cells of glial lineages are thought to preferentially undergo malignant transformation after transplacental exposure to ethylnitrosourea (EtNU). We recently have reported that monoclonal antibody (mAb) RB13-6 recognizes a developmentally regulated 130 kDa cell surface glycoprotein (gp130RB13-6) transiently expressed by a small subpopulation of glial progenitor cells in pre-natal rat brain. The expression of gp130RB13-6 has now been analysed immunocytochemically in malignant gliomas induced on day 15, 18 or 21 of gestation and in long-term cultures of fetal brain cells (FBC) isolated after in vivo-exposure to EtNU on day 18 of gestation. Malignant gliomas induced at different gestational stages contained varying proportions of gp130RB13-6-positive cells, whereas a subpopulation of proliferative neural progenitor cells exhibiting sustained gp130RB13-6 expression persisted in long-term FBC cultures after 3 months. This subpopulation, which was not selected for in control cultures of FBC derived from buffer-treated rats, gave rise to malignant cell lines after a period of time similar to the latency period required for glioma development in vivo. These data suggest that gp130RB13-6-positive cells of the immature rat nervous system may represent a subset of neural progenitor cells particularly susceptible to the oncogenic effect of EtNU.