Regional and developmental changes in metabolite concentrations were measured by 1H NMR spectroscopy and HPLC of perchloric acid extracts from rat brain and eye. The highest concentrations of N-acetylaspartate were found in grey matter as opposed to white matter with concentration increasing with age from neonate to adult, while the related compound N-acetylaspartylglutamate was highest in adult optic nerve. Creatine and choline-containing compounds were present in all regions throughout development, with higher levels of creatine found in grey matter compared to other regions. Choline-containing compounds were present at the highest concentrations in the eye at all ages examined, and tended to decrease in concentration to minimum values in adulthood in all regions. The presence of hypotaurine in corpus callosum and optic nerve was consistent with the metabolic profiles of O-2A progenitor cells and oligodendrocytes, which are cells composing these tissues. The neurotransmitters glutamate and GABA reached their highest concentrations in the olfactory bulb (higher than in adult cortex).

Cell culture techniques, high-resolution in vitro 1H NMR spectroscopy, and chromatographic analyses were used to compare the properties of three types of human brain and nervous system tumours. Cell lines were immunocytochemically characterized at all stages in culture with specific antibodies. Intracellular metabolites present in cell extracts were analysed by 1H NMR spectroscopy and by high performance liquid chromatography (HPLC). The spectra from meningiomas, neuroblastomas, and glioblastomas displayed, in addition to similarities-including the presence of signals from leucine, isoleucine, valine, threonine, lactate, acetate, glutamate, choline-containing compounds and glycine-certain distinguishing metabolic features. Spectra from meningiomas featured relatively high signals from alanine. Intense signals from creatine were present in neuroblastoma spectra, while in spectra from glioblastoma they were not detectable. We found statistically significant differences by 1H NMR spectroscopy in the amounts of alanine, glutamate, creatine, phosphorylcholine and threonine among the types of tumours examined. HPLC determinations confirmed that there were also other metabolites specific to a type of tumour, such as taurine, gamma-aminobutyric acid, and serine. We suggest that these findings have potential relevance for the development of non-invasive diagnosis of tumour lineage by 1H NMR spectroscopy in vivo.

Summary Well-characterized cell lines established from primitive neuroectodermal tumours (PNETs) were examined by proton nuclear magnetic resonance ('H-NMR) spectroscopy and chromatographic analysis of perchloric acid extracts, following amplification in cell culture. A characteristic 'H-NMR spectroscopic metabolite pattern was found for medulloblastoma cell lines, which clearly discriminates these cells from PNETs of other locations in the central nervous system (CNS), on the basis of their N-acetyl aspartate (NM) and aspartate expression. Medulloblastoma cell lines were heterogeneous in respect of their metabolite expression, possibly owing to the heterogeneity in their differentiation along lineages of the CNS. All PNET spectra displayed similar features, including decreased NAA and creatine peaks and increased signals from choline compounds (Cho) compared with normal cerebellum. The expression of NM by the medulloblastoma lines was in the opposite order to the extent of neuronal differentiation, which may indicate their origin from a progenitor cell with the phenotype of an oligodendrocyte-type-2 astrocyte cell.Keywords: human primitive neuroectodermal tumour; human medulloblastoma; proton nuclear magnetic resonance spectroscopy; metabolite; cell line Primitive neuroectodermal tumours (PNETs) are highly malignant [grade IV according to the World Health Organization classification of brain tumours by Kleihues et al (1993)] and among the most common tumours of childhood. They are most frequently located in the cerebellum (i.e. cerebellar medulloblastomas), but tumours that have a similar appearance and biological behaviour have been found in other locations in the central nervous system (CNS), such as the cerebrum, pineal region or spinal cord. The nature and cell of origin of these tumours, composed of primitive or undifferentiated neuroepithelial cells, is controversial. Questions have been raised as to whether their cell of origin is unique to the portion of the CNS in which the tumour arises, or whether there is a primitive or undifferentiated cell common to all portions of the CNS. Rorke et al (1985) have suggested that these tumours arise from a single primitive multipotential cell that has the capacity to differentiate into one or more types of neural cellssuch as astrocytes, oligodendrocytes, neurons, ganglion cells or melanocytes -and are therefore regarded as malignant counterparts of multipotential neural progenitor cells.Progress in understanding the cell biology of these tumours has been hampered by the lack of cultured cell lines, since relatively few continuous medulloblastoma lines have been established thus far (Friedman et al, 1985;Jacobsen et al, 1985). However, the recent establishment of five new human PNET cell lines from surgical specimens (Pietsch et al, 1994) Correspondence to: S Williams investigate the biology, phenotype, lineage and metabolism of PNETs in detail. In the present study, metabolite profiles of several of these PNET cell lines in culture, together with two establishe...