The effect of dietary tyrosine and phenylalanine on survival of adult female C57BL/6 × DBA/2 F, mice bearing i.p. slow-growing, moderately pigmented and fast-growing, highly pigmented B16 melanoma tumors was studied alone and in combination with carbidopa-levodopa methyl ester chemotherapy. These studies tested three different diets: a natural product diet containing 1.09% phenylalanine and 0.64% tyrosine (commercial diet); a chemically defined crystalline amino acid diet containing 0.6% phenylalanine and 0.3% tyrosine (purified diet); and a nutritionally deficient chemically defined diet conaining 0.08% phenylalanine and 0.04% tyrosine (deficient diet). Mice received carbidopa (100 mg/kg) and levodopa methyl ester (1000 mg/kg) i.p. daily for 12 days.

The median survival of mice bearing the slow-growing tumor averaged 8 days longer than that of mice bearing the fast-growing tumor. Median survival increased by 42% (slow-growing tumor) and by 30% (fast-growing tumor) in mice maintained on the deficient diet. Drug treatment significantly increased survival in mice maintained on the purified and deficient diets but was relatively ineffective in mice maintained on the commercial diet regardless of the tumor growth characteristics. The largest increases in median survival of 61% (slow-growing tumor) and of 78% (fast-growing tumor) occurred in the treated mice maintained on the deficient diet. Plasma tyrosine and phenylalanine levels decreased by 33 and 21%, respectively, in mice maintained on the deficient diet and were unaffected by drug treatment. Tumors were 60% smaller in mice maintained on the deficient diet compared to mice maintained on the purified diet.

Drug treatment resulted in decreased food intake and weight loss in all tumor-bearing dietary groups. Restricting food intake in untreated tumor-bearing mice to the amounts consumed by the drug treatment groups resulted in a parallel loss in body weight but no significant alteration in median survival. These data show that concomitant dietary tyrosine-phenylalanine restriction enhances the antitumor activity of carbidopa-levodopa methyl ester against B16 melanoma.

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These studies were supported in part by funds provided to Washington State Iniversity through the NIH Biomedical Research Support Grant and by funds from the National Cancer Institute Grant CA 26533 and the American Cancer Society Grant PDT-166.

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