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.