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Therapeutic Tumor-specific Cell Cycle Block Induced by Methionine Starvation in Vivo¹

Anticancer, Inc., 7917 Ostrow Street, San Diego, California 92111 [H. G., V. K. L., H. H., A. G., R. M. H.]; Laboratory of Cancer Biology, University of California, San Diego, La Jolla, California 92093-0609 [R. M. H.]; and Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku Ku, Tokyo 160, Japan [T. K.]

² To whom requests for reprints should be addressed.

The ability to induce a specific cell cycle block selectively in the tumor could have many uses in chemotherapy. In the present study we have achieved this goal of inducing a tumor-specific cell cycle block in vivo by depriving Yoshida sarcoma-bearing nude mice of dietary methionine. Further, we demonstrate that methionine depletion also causes the tumor to eventually regress. The antitumor effect of methionine depletion resulted in the extended survival of the tumor-bearing mice. The mice on the methionine-deprived diets maintained their body weight for the time period studied, indicating that tumor regression was not a function of body weight loss. The data reported here support future experiments utilizing methionine depletion as a target for tumor-selective cell cycle-dependent therapy.

¹ This study was supported by National Cancer Institute SBIR Grant R44CA43444 and National Cancer Institute Grant R01CA27564.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 7/12/93. Accepted 9/27/93.

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