OPTIMAL 06-BENZYLGUANINE DOSE FOR DNA ALKYLTRANSFERASE DEPLETION

$0M01FY2000RRNIH

University Of Chicago, Chicago IL

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Abstract

The DNA repair protein, O6-alkylguanine-DNA alkyltransferase plays an important role in the protection of cells from the cytotoxic effects of chloroethylating agents and methylating agents, thereby limiting the clinical utility of these drugs in the presence of this protein. The proposal is designed to determine the minimal O6-BG dose at which there is at least a depletion of tumor AGT activity to less than 10 fmol/mg protein at a specified time post-O6BG in patients with surgically resectable solid tumors. Also, to correlate tumor tissue AGT depletion in PBMCs obtained at a specified time-point after O6-BG administration. Patients with cancer with surgically resectable disease will receive a single dose infusion of O6-BG, diluted in 150 cc D5W and infused intravenously for over one hour.

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