ENHANCEMENT OF ANTITUMOR ACTIVITY OF ARABINOFURANOSYLADENINE BY 2'-DEOXYCOFORMYCIN

Abstract

The 6C3HED lymphosarcoma, a tumor cell line very sensitive to 9-.beta.-D-arabinofuranosyladenine(ara-A) and 6C3HED/ara-A, a line resistant to ara-A, were studied. Both were responsive to 9-.beta.-D-arabinofuranosylcytosine (ara-C). Two lines of cells, L1210 and L1210/ara-C, were both resistant to ara-A and had very high levels of the deaminase that inactivated ara-A. When an effective inhibitor of the deaminase, 2''-deoxycoformycin, was combined with ara-A in the treatment of mice bearing L1210 or L1210/ara-C tumors, both became responsive to ara-A. Studies are reported on the extent of effects of 2''-deoxycoformycin at several dose levels and the duration of its effects in tumor cells and normal tissues. Single doses produced essentially complete inhibition of the deaminase, and little recovery was seen before 24 h. DNA synthesis in normal tissues recovered more quickly. ara-A and ara-C, the former as a new derivative (9-.beta.-D-arabinofuranosyladenine 5''-phosphate, and possibly combined with 2''-deoxycoformycin, could be regarded as potentially alternative drugs for the treatment of neoplasms.