In vivo magnetic resonance spectroscopy (MRS) has revealed that phosphomonoesters (PME) such as
phosphocholine (
PCho) and
phosphoethanolamine (PEth) are elevated in
tumors and rapidly proliferating tissues. The regulation of PME levels and their relationship to proliferation are not well known. In the present study, we investigated the regulation of
PCho and PEth levels in rat
glioma cells grown in vivo and in vitro using 31P and 13C MRS. However, the ability of cells to produce
choline endogenously is variable. To fully understand regulation of
PCho levels, it is necessary to characterize the activity of the endogenous pathway, if it exists. This was first investigated by following the metabolic fate of 13C-labeled
methionine of 9L
glioma tumors in vivo. Our results indicate that there is a significant amount of de novo
choline synthesis in vivo. However, similar experiments performed in vitro using cells cultured in
bioreactors indicated that
glioma cells themselves are unable to synthesize
choline de novo, suggesting that the in vivo results were due to the involvement of extra-tumoral organs, e.g., liver. Further in vitro experiments demonstrated that the uptake and phosphorylation of physiologically relevant concentrations of exogenous
choline is very active in these systems. Thus, it appears that the exogenous pathway for
PCho biosynthesis predominates and regulates
PCho levels in
glioma cells. Our results also demonstrate that
PCho levels are lowest, and PEth levels are highest, in non-proliferating cells. These observations indicate that there is a decrease in the biosynthesis of
PCho concomitant with a reduction in culture growth. The source of the increased PEth is, as yet, undefined.