PMID: 1206744Nov 1, 1975Paper

Neoplastic transformation of fetal rat brain cells in culture after exposure to ethylnitrosourea in vivo

Journal of the National Cancer Institute
O D Laerum, M F Rajewsky

Abstract

A single, transplacental pulse of N-ethyl-N-nitrosourea (ENU; 75 mug/g body wt) to the fetal (18th day of gestation) BD IX rat led to death with malignant tumors of the central and peripheral nervous system after a median time of approximately 195 days. In contrast to untreated control cells, dissociated brain cells transferred to long-term cell culture 20-90 hours after the ENU pulse became tumorigenic after approximately 200 days, as assayed by reimplantation into baby BD IX rats. This was preceded by a characteristic sequence of phenotypic alterations (termed "stages I-IV"). During early primary culture (stage I), both ENU and control cultures exhibited stationary glia-like cells on a growing layer of epithelioid (possibly glia precursors) and few fibroblast-like cells. Stage II (approximately 10th-40th day) was characterized by a constant proportion of glia-like cells in the ENU cultures and by their disappearance in the controls. During stage III (approximately 40th-100th day), slowly proliferating glia-like cells in the ENU cultures formed "piled-up" foci. They could then be removed from the underlying cell layer and cultured separately. Transition to stage IV (approximately 100th-200th day) was marked by proliferation of...Continue Reading

Citations

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