Depletion of serum methionine by methioninase in mice.

Methionine dependence is a tumor-specific metabolic defect found in human cancer cell lines as well as in fresh human tumor specimens. Methionine dependent tumors cease growing when deprived of methionine, unlike normal cells which can substitute homocysteine for methionine for their growth requirement. We have previously purified a stable, endotoxin-free methioninase from the bacterium, Pseudomonas putida. We demonstrate in this report that purified methioninase can lower the serum levels of methionine in normal and nude mice from 60 microM to approximately 5 microM within 1 hour. The circulating half-life of methioninase is approximately 100 minutes in mice after i.v. injection. The enzyme therefore seems to be a good candidate as an antitumor agent for methionine-dependent tumors.