RESISTANCE TO 9-BETA-D-ARABINOFURANOSYLADENINE IN MURINE TUMOR-CELLS

  • 1 January 1978
    • journal article
    • research article
    • Vol. 38  (8) , 2314-2316
Abstract
Two lines of 6C3HED (Gardner mouse lymphosarcoma), 6C3HED-LeP and 6C3HED-ADL, were studied [in vivo]. The former is exquisitely sensitive to 9-.beta.-D-arabinofuranosyladenine (ara-A) and the latter is resistant. Cytological examinations and strain specificity tests indicated that they were both 6C3HED. DNA synthesis in the sensitive line was more sensitive to ara-A in whole-cell incubations than it was in the resistant line. In cell-free extracts, the DNA synthesis of the sensitive line showed greater inhibition by 9-.beta.-D-arabinofuranosyladenine 5''-triphosphate. Lower ability to form 9-.beta.-D-arabinofuranosyladenine 5''-triphosphate or to allow access to the intracellular space was eliminated as an explanation for the resistance. Cells from an ara-A-resistant human leukemia were tested, and the DNA synthesis of of the cells, in either whole cells or cell-free extract, was unaffected by ara-A or 9-.beta.-D-arabinofuranosyladenine 5''-triphosphate, respectively. Resistance apparently has emerged by reason of change in the DNA polymerase(s). The finding may be important in the clinical use of ara-A.