AbstractVariants resistant to 2‐deoxy‐D‐glucose have been isolated from a clonal line of pig kidney cells by serial cultivation in the presence of inhibitor. Hexokinase activity may be affected directly in this system, since the oxidation of glucose to 6‐phosphogluconate by extracts from sensitive and resistant cells is blocked by the addition of 2‐deoxy‐glucose to the reaction mixture. This blockage was removed by the addition of glucose‐6‐phosphate to the system, but not by ATP. Resistant cells were found to accumulate significantly less 2‐deoxyglucose‐6‐phosphate than sensitive cells. The rate of phosphorylation of 2‐deoxyglucose, however, was higher in extracts from the resistant line. Alkaline phosphatase does not account for the reduced level of 2‐deoxyglucose‐6‐phosphate since this enzyme is not detectable in sensitive or resistant pig kidney cells. Increased acid phosphatase activity was observed in resistant cells, but extracts with high acid phosphatase activity proved incapable of hydrolyzing either 2‐deoxyglucose‐6‐phosphate or glucose‐6‐phosphate. In comparative growth studies, cells resistant to 2‐deoxyglucose proliferated more extensively than sensitive cells in a low glucose nutrient. They removed glucose more effectively from this medium, and were less stimulated by the addition of intermediates from the tricarboxylic acid cycle. The evidence suggests that resistance to 2‐deoxyglucose in the cells under study may be based on the ability of the resistant cells to proliferate at concentrations of glucose too l
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