Cellular environment in the liver of tumor-bearing rats: a 13C NMR study

Although hepatic metabolism is known to be altered in the presence of a remote tumor, it is unclear whether the alterations are brought on by changes in cellular conditions or dysfunction of enzymes. Chemical shifts of 13C NMR spectral peaks are known to vary depending on the physical conditions within the molecular environment, such as pH, electrolyte concentrations and temperature. In the present study, we examined the responsiveness of 13C NMR peak positions to different experimental conditions by comparing chemical shifts of metabolite peaks in perfused and extracted livers. The sensitivity of the technique was confirmed by observing chemical shift differences between these two experimental conditions of the amino carbons (C-2's) of glutamate, glutamine, N-carbamoylaspartate and aspartate. Subsequently, 13C NMR spectroscopy was employed to detect changes in the cellular environment in the livers of tumor-bearing rats. Minimal alterations in peak locations for intracellular metabolites were found in the presence of a distant tumor. This indicates that the overall cellular environment is not significantly altered by the presence of a distant tumor. Therefore, the known alterations in hepatic metabolism of tumor hosts are probably brought on by enzymatic abnormalities rather than changes in the cellular milieu. In addition, comparison of peak positions with other published reports were made, and the extent of unexplained chemical shift variations between biological studies is discussed.