CYTOXICITY OF -DICHLORO-9A-N-PROPYL-2,3,9,9A-TETRAHYDRO-3-OXO-1H FLUOREN-7-YL)OXY] ACETIC-ACID, AN AGENT KNOWN TO REDUCE BRAIN EDEMA

A known agent, -dichloro-9a-n-propyl-2,3,9,9a-tetrahydro-3-oxo-1H fluo ren-7-yl)oxy]acetic acid, which blocks brain edema, was also shown to be a potent cytotoxic agent in leukemia cells. The major site of actio n of the agents appears to be in the de novo purine synthetic pathway in L1210 leukemic cells. Both PRPP amido transferase and IMP dehydroge nase activities were suppressed by the agent. The inhibition of both r egulatory enzymes of the pathway along with the reduction of dihydrofo late reductase activity would account for the observed suppression of DNA and RNA syntheses and subsequent cancer cell death.