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Cellular Accumulation of Methylglyoxal-bis-guanylhydrazone in Vitro

II. Studies on the Mechanism of Accumulation in Leukemic Leukocytes^*

( Laboratory of Chemical Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland)

The influence of incubation medium pH on MeGAG uptake into leukemic leukocytes suggests that the cationic form of the drug is transported or bound intracellularly. A large intra- to extracellular potassium gradient is essential to concentrative MeGAG uptake. Preloading leukocytes with MeGAG does not alter subsequent tracer uptake. There is almost no efflux of MeGAG from leukocytes in the cold. Efflux at 37°C. is greater, suggesting active MeGAG extrusion from cells. The data on influx and efflux presented in this report suggest both active membrane transport and intracellular binding of MeGAG.

^* Presented in part at the annual meeting of the American Association for Cancer Research, Toronto, Canada, May, 1963, and published in abstract form in Proc. Am. Assoc. Cancer Res., 4:6, 1963.

Received 6/15/64.