Effect of DL-Buthionine-S,R-sulfoximine on the Growth of EMT6 and RIF Mouse Tumors 1,2

A8STRACT-The response of murine EMT6 and RIF tumors to DL-buthionine-S,R-sulfoximine (8S0), a glutathione (GSH) depletor, given either as a single dose, continuous oral administration, or in multiple doses, was determined with the use of a tumor-growth-delay assay. 8S0 consistently caused significant tumor growth delay in EMT6 tumors, which reached 5-7 days (two doubling times) after a single 8S0 dose (40 Jlmollkg or 4 mmollkg), 3 days (one doubling time) with continuous oral administration (20 mM), and 9 days (three doubling times) with daily 8S0 administrations (4 mmol/kg) starting at the time of tumor inoculation. Growth inhibition persisted after discontinuation of 8S0 treatment. Some complete tumor regressions were observed. Only slight tumor growth delay (one doubling time) was observed in RIF tumors at all treatment modes. No direct correlation was observed between tumor GSH content and the effects on tumor growth. In vitro 8S