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Intracellular Activation of -L-Glutaminyl-4-hydroxybenzene by Tyrosinase, a Mechanism for Selective Cytotoxicity against Melanocarcinoma¹

Department of Pathology Duke University Medical Center [F. S. V., L. A. K. K., K. B., D. G. G.] and Department of Chemistry Duke University [P. W. J.] Durham, North Carolina 27710

In the presence of tyrosinase, the phenol -L-glutaminyl-4-hydroxybenzene is oxidized to a quinone that strongly inhibits metabolism of neoplastic cells in vitro. Conceptually, this enzymatic dependency could initiate specific cytotoxicity in vivo directed to cells that contain tyrosinase. In tests of this hypothesis, the injection of -L-glutaminyl-4-hydroxybenzene with probenecid significantly inhibited the growth of human melanoma in athymic mice without apparent toxicity to the cells of the host that lack the enzyme.

¹ This investigation was supported in part by Grant CA 19013 awarded by the National Cancer Institute.

Received 10/ 3/78. Accepted 1/26/79.