Transmission electron microscopy of fetal rat brain cells during neoplastic transformation in cell culture

Fetal rat brain cells were investigated by transmission electron microscopy during neoplastic transformation in long-term cell culture. Before transfer of the cells to culture, BD IX rat fetuses were treated with a single transplacental pulse of N-ethyl-N-nitrosourea (75 micrograms/g body wt) on the 18th day of gestation. During the early stages (3--4 mo), both glia-like and neuron-like cells were present in the culture, and after 2 months they formed complex aggregates ("nodules"). In contrast, corresponding secondary control cultures consisted of flat, epithelioid neural cells without neuron or astrocyte differentiation. After 3 months, cells with neuron morphology gradually disappeared. Some of the remaining cells contained many autophagosomes. After 5 months, rapid proliferation of rather homogeneous, glia-like populations was accompanied by reduction of microfilament bundles and microtubules, as well as atypical nuclei. Ability to form tumors upon sc implantation into syngeneic hosts was not observed until about 3 months later.