PHOSPHOMONOESTER METABOLISM AS A FUNCTION OF CELL PROLIFERATIVE STATUS AND EXOGENOUS PRECURSORS

Elevations of phosphomonoesters (PMEs) correlate with increased cell g rowth or increased cell degradation, and have been shown to occur in h uman tumors as well as animal tumor models and cell lines. Furthermore , decreased PME levels have been observed in tumor patients who respon d to the therapy. Therefore, understanding the mechanisms underlying t he interactions of intrinsic and extrinsic control of PMEs may assist diagnosis and treatment of tumors at the clinical level. In order to p robe the underlying mechanisms controlling PME concentrations, we used cells grown in bioreactors and P-31 nuclear magnetic resonance spectr oscopy to study the effects of proliferative status and exogenous prec ursor amines on the PMEs phosphorylcholine (PCho) and phosphorylethano lamine (PEtn). In general, PEtn demonstrated an inverse correlation wi th cell growth, beginning to rise as the stationary growth phase was a pproached. PCho, on the other hand, generally decreased during log gro wth, an effect that was reversed by the addition of exogenous choline. The net effect of these changes consistent and dramatically lower PCh o/PEtn ratio in stationary cultures compared to actively proliferating cultures.