Enhancement of the antitumor activity of arabinofuranosyladenine of 2'-deoxycoformycin.
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, are both resistant to ara-A and have very high levels of the deaminase that inactivates 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 effect in tumor cells and normal tissues. Single doses produce essentially complete inhibition of the deaminase, and little recovery was seen before 24 hr. However, DNA synthesis in normal tissues recovered more quickly. It is suggested that ara-A and ara-C, the former as a new derivative (9-beta-D-arabinofuranosyladenine 5'-phosphate) and possibly combined with 2'-deoxycoformycin, be regarded as potentially alternative drugs for the treatment of neoplasms.
D000243:Adenosine Deaminase / Q000378:metabolism; D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D001381:Azepines / Q000494:pharmacology* / Q000627:therapeutic use; D003561:Cytarabine / Q000627:therapeutic use*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D003853:Deoxyribonucleosides / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004357:Drug Synergism; D005260:Female; D007939:Leukemia L1210 / Q000188:drug therapy / Q000201:enzymology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D011684:Purine Nucleosides / Q000494:pharmacology*; D012513:Sarcoma, Experimental / Q000188:drug therapy; D014740:Vidarabine / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use
D058892:Adenosine Deaminase Inhibitors; D001381:Azepines; D004273:DNA, Neoplasm; D003853:Deoxyribonucleosides; D011684:Purine Nucleosides; D003561:Cytarabine; D000243:Adenosine Deaminase; D014740:Vidarabine