Inhibitory effect of L-methionine-deprived amino acid imbalance using total parenteral nutrition on growth of ascites hepatoma in rats

Abstract

The antitumor effect of an amino acid imbalance characterized by the absence of L-methionine was investigated in AH-109A ascites hepatoma-bearing rats with the technique of total parenteral nutrition (TPN). A central venous catheter was placed at the superior vena cava of the rat and hypertonic glucose solution plus an amino acid mixture, an ordinary amino acid compound but lacking L-methionine and L-cysteine, was administered as protein source for seven days. Increases in the volume of ascites and the number of tumor cells were significantly inhibited in the rats receiving glucose plus L-methionine-free amino acid mixture compared to the control rats given glucose only, glucose plus ordinary amino acid mixture and laboratory rations. Unfavorable side effects of TPN with amino acid compound lacking L-methionine and L-cysteine were loss of body weight and development of hypoproteinemia. No evidence of hepatic injury and bone marrow suppression due to this treatment were obtained from the results of biochemical and hematological studies. In liver cells and ascites tumor cells, morphologically, prominent enlargement of the nucleoli was observed in the rats treated with the amino acid mixture lacking of L-methionine and L-cysteine.