alanosine and 2-(methylamino)isobutyric-acid

In previous studies, we observed decreased uptake of 14C-labeled L-aspartate and L-glutamate in s.c. transplants of several rapidly growing hepatomas relative to that in normal liver. The present report extends these observations to isolated cells and indicates that circulation differences cannot be the major factor. Mean net uptakes for the two dicarboxylic amino acids in cells from the rapidly growing Morris Hepatomas 7288ctc and 7777 were 5 to 26% of corresponding values for normal hepatocytes. Rates for net uptake in Hepatoma 7787 cells were intermediate between those of the rapidly growing hepatomas and hepatocytes, while the rates for Hepatoma 5123C cells and hepatocytes were similar. The contribution of sodium-dependent uptake to the mean total net uptake of [14C]aspartate and [14C]glutamate tended to be higher in hepatoma cells than in hepatocytes. Studies with isolated hepatocytes and Hepatoma 5123C cells showed no significant effect on uptake by 10 mM alpha-(methylamino)isobutyric acid and 10 mM 2-amino-2-carboxybicyclo[2.2.1]heptane. On the other hand, L-cysteic acid, L-alanosine, and N-phosphonacetyl-L-aspartic acid were shown to be effective inhibitors of sodium-dependent uptake in Hepatoma 5123C cells. The data suggest that the A and L systems are not major contributors to the uptake of dicarboxylic amino acids in hepatic cells. It was concluded that decreased uptake of dicarboxylic amino acids in rapidly growing hepatomas may accompany decreased metabolism of these dietary nonessential amino acids.

Topics: Alanine; Amino Acids; Amino Acids, Cyclic; Amino Acids, Dicarboxylic; Aminoisobutyric Acids; Animals; Antibiotics, Antineoplastic; Aspartic Acid; Liver; Liver Neoplasms, Experimental; Male; Nitrosamines; Phosphonoacetic Acid; Rats; Sodium