BIOCHEMICAL MODULATION OF TUMOR-GROWTH, METASTASIS AND HOST METABOLISM

Exogenous nutrients, hormones and metabolites can significantly alter tumor growth, metastasis, and host nutritional status. Arginine, serin e and methionine are critical amino acids required for protein, DNA an d RNA synthesis and, thus, for cellular proliferation. To determine th e effect of these specific amino acids on host metabolism, primary tum or growth and metastasis, 48 Lewis rats bearing the mammary adenocarci noma MAC-33 were randomized to receive similar diets with 3% supplemen ts of serine, arginine, methionine or glycine (control). After 25 days on each diet, animals were sacrificed to determine primary tumor bioc hemical composition and growth kinetics, number of lung metastases and carcass weight. A significant reduction in lung metastases occurred w ith serine and methionine supplementation (p<0.01) with no significant change in primary tumor size. However, increased mortality (p<0.001) and low carcass weight (p<0.05) were found in the methionine group ind icating significant host toxicity. Serine-supplemented animals had a m ortality rate and carcass weight comparable to the control group. Argi nine supplementation had no effect on primary tumor growth, metastasis or carcass weight; however, increased mortality was observed in this group compared to controls. These results suggest that serine suppleme ntation selectively supports host growth and inhibits metastasis in tu mor-bearing animals. This study demonstrates the potential to differen tially effect host and tumor growth with exogenous amino acid suppleme nts.