Improved host defense against L1210 leukemia by deprivation of dietary phenylalanine

Restriction of phenylalanine to 0.08%, or less, of the diet has been shown to prolong the survival of L1210 leukemia-bearing DBA/2Ha mice or (DBA/2Ha female X BALB/c male) F1 hybrids. A clonal assay was developed for determining the infiltration of L1210 cells without adaption to cell culture. Phenylalanine restriction significantly reduced at the infiltration of IP implanted tumors in tissues of minimal tumor involvement, such as bone marrow and brain. These tumor reductions did not occur with dietary limitations of isoleucine, leucine, cystine-methionine or protein. Tumor infiltration rose to control levels when phenylalanine-limited hosts were immunosuppressed with whole body irradiation or with cyclophosphamide. The L1210-responding BALB/c host when phenylalanine-restricted required a 2- to 3-fold increase in dosage of whole body irradiation in order to succumb to the tumor. In vitro complement-dependent and -independent cytotoxicity of the splenocytes of several host strains immunized to both L1210 cells and sheep erythrocytes were, however, generally reduced by phenylalanine depletion. Phenylalanine depletion is postulated to favor the development of an unidentified immunoproductive and radiation-resistant component of host tumor response.