Surface antigens of cell subpopulations in prenatal rat brain are expressed in a characteristic non-random pattern on their ethylnitrosourea-induced malignant counterparts

Abstract

Abstract Selective induction of neural tumors in the rat by single-dose exposure of the immature nervous system to ethylnitrosourea (EtNU) is a model for the study of cell lineage-, differentiation stage-, and carcinogen-dependent mechanisms in neuro-oncogenesis. Overall yields and relative frequencies of different types of neural tumors vary with the developmental window chosen for the EtNU-pulse. Precursor cells belonging to different neural lineages and targeted by the carcinogen at distinct developmental stages may thus bear a differential risk of malignant conversion. To specify subpopulations of neural precursors in fetal (prenatal day 18) BDIX-rat brain, four monoclonal antibodies (mAbs) recognizing cell surface differentiation antigens were used: mAb RB13–2 directed against O-acetylated gangliosides and binding to approximately 36% of fetal brain cells (FBC); mAb RB13–6 recognizing a 130 kDa glycoprotein (expressed by approximately 8% of FBC); and mAbs RB21–7 and RB21–15 which bind, respectively, to embryonal neural cell adhesion molecules (N–CAM) and a 24 kDa protein (expressed by approximately 55% and 12% of FBC). Antigen expression profiles were compared with those of 14 primary brain tumors and 16 malignant neural cell lines, all of which had been induced by EtNU on prenatal day 18 in vivo. Monoclonal antibodies RB13–2 and RB21–7 did not bind to any of the tumors or cell lines. In contrast, mAbs RB13–6 and RB21–15 both reacted with 14/14 tumors, and with 16/16 and 10/16 cell lines, respectively. Expression of the latter antigens might thus specify lineage-specific stages of FBC development/differentiation particularly susceptible to EtNU-induced malignant transformation. Two-color fluorescence analyses revealed three subsets of FBC binding mAb RB13–6 (RB13–2 +/ RB13–6 +/ RB21–15 −; RB13–2 −/RB13–6 +/RB21–15 −; and RB13–2 −/ RB13–6 +/RB21–15 +), representing successive stages of differentiation.