Effect of Low Phenylalanine Diet on Murine Leukemia L1210 2

Publisher Website
Google Scholar
Abstract
Survival of inbred DBA/2 mice or F, hybrids bearing ascites L1210 leukemia or P288 leukemia could be prolonged if phenylalanine (Phe) intake was moderately restricted to 0.08% of the diet. Several lines of evidence indicated that diet acted against L1210 tumors by potentiating host defense rather than by starving tumors directly. Diet lowered the rate of ascites L1210 cell accumulation by 15%. This minor growth inhibition was retained upon host pre irradiation with 100-250 rads, but host protection was abolished. Implanted non immune splenocytes also antagonized dietary protection. Both antagonisms were interpreted in terms of immunosuppression. Adoptive immunity was examined with splenocytes from cured hosts or from mice primed with irradiated L1210 cells. Splenocyte recipients survived L1210 tumor longer when the donor, recipient, or both were fed on limited, ineffective diet schedules. Immune potentiation could thus be produced by diet without direct inhibition of L1210 tumor. In host and tumor subllnes, diet effects correlated with Immunogenlclty. Thus diet was completely curative in (BALB/c♀ x DBA/2HaDD♂)F, hosts with L1210 tumors and optimally doubled survival times of inbred DBA/2HaDD hosts with L1210 tumors; however, it was effective in syngeneic DBA/2 hosts only against the more immunogenic subllne L1210/GZL. Diet was protective even if started after L1210 tumor implantation. Prolongation of host survival was greatly reduced or abolished if, in separate modifications the diet was discontinued, the tyrosine level was lowered additionally to 0.04%, the Phe level was changed to 0 or 0.36%, ammonia lyase was coadministered, or weight losses were matched with restricted chow diet. Serum Phe levels fell below half-normal levels after a week of diet. L1210 eell growth initially faeilitated but later tended to reverse this fall.