Effect of long‐term depletion of plasma methionine on the growth and survival of human brain tumor xenografts in athymic mice

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Abstract
Depletion of plasma methionine is expected to inhibit or reverse growth of methionine‐dependent tumors; however, modulation of methionine and other sulfur amino acids is not a trivial task in experimental animals. l‐Methioninase from Pseudomonas putida at 1,000 U/kg causes acute reduction of plasma methionine by 80% in mice, but recovery occurs within 14 hours. Restriction of dietary choline and replacement of dietary methionine with homocystine results in 50% chronic reduction of plasma methionine. A >70% reduction can be accomplished with a diet deficient in methionine, homocystine, and choline, but ultimately this diet is lethal. Plasma methionine can be lowered to a steady state of

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