Phosphohydrolase activity was examined in cell-free extracts of Sarcoma 180 and a subline (Sarcoma 180/TG) resistant to both 6-mercaptopurine and 6-thioguanine as well as their respective nucleosides. Acid phosphohydrolase and soluble 5′-nucleotidase activities were identical in the two cell lines, whereas alkaline phosphohydrolase activity was 8 times greater in Sarcoma 180/TG. Alkaline phosphohydrolase activity was localized predominantly in particulate fractions from Sarcoma 180/TG, showed a pH optimum of 9.2, and hydrolyzed a wide variety of phosphate esters, including p-nitrophenylphosphate and 5′-nucleotides, such as 6-thioinosine 5′-phosphate. It is suggested that enhanced breakdown of the active nucleotide form of the 6-thiopurines by alkaline phosphohydrolase is at least partially responsible for the insensitivity of Sarcoma 180/TG to these agents.

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This study was supported by Grant CA-02817 from the National Cancer Institute, USPHS, and Grant T-23 from the American Cancer Society.

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