SURFACE-ANTIGENS OF CELL SUBPOPULATIONS IN PRENATAL RAT-BRAIN ARE EXPRESSED IN A CHARACTERISTIC NONRANDOM PATTERN ON THEIR ETHYLNITROSOUREA-INDUCED MALIGNANT COUNTERPARTS

Selective induction of neural tumors in the rat by single-dose exposur e of the immature nervous system to ethylnitrosourea (EtNU) is a model for the study of cell lineage-, differentiation stage-, and carcinoge n-dependent mechanisms in neuro-oncogenesis, Overall yields and relati ve frequencies of different types of neural tumors vary with the devel opmental window chosen for the EtNU-pulse. Precursor cells belonging t o different neural lineages and targeted by the carcinogen at distinct developmental stages may thus bear a differential risk of malignant c onversion. To specify subpopulations of neural precursors in fetal (pr enatal day 18) BDIX-rat brain, four monoclonal antibodies (mAbs) recog nizing cell surface differentiation antigens were used: mAb RB13-2 dir ected against O-acetylated gangliosides and binding to approximately 3 6% of fetal brain cells (FBC); mAb RB13-6 recognizing a 130 kDa glycop rotein (expressed by approximately 8% of FBC); and mAbs RB21-7 and RB2 1-15 which bind, respectively, to embryonal neural cell adhesion molec ules (N-CAM) and a 24 kDa protein (expressed by approximately 55% and 12% of FBC). Antigen expression profiles were compared with those of 1 4 primary brain tumors and 16 malignant neural cell lines, all of whic h had been induced by EtNU on prenatal day 18 in vivo. Monoclonal anti bodies RB13-2 and RB21-7 did not bind to any of the tumors or cell lin es. In contrast, mAbs RB13-6 and RB21-15 both reacted with 14/14 tumor s, and with 16/16 and 10/16 cell lines, respectively. Expression of th e latter antigens might thus specify lineage-specific stages of FBC de velopment/differentiation particularly susceptible to EtNU-induced mal ignant transformation. Two-color fluorescence analyses revealed three subsets of FBC binding mAb RB13-6 (RB13-2(+)/ RB13-6(+)/RB21-15(-); RB 13-2(-)/RB13-6(+)/RB21-15(-); and RB13-2(-)/RB13-6(+)/RB21-15(+)), rep resenting successive stages of differentiation.