POTENTIATION BY 2'-DEOXYCOFORMYCIN OF INHIBITORY EFFECT BY 3'-DEOXYADENOSINE (CORDYCEPIN) ON NUCLEAR-RNA SYNTHESIS IN L1210-CELLS INVITRO

  • 1 January 1978
    • journal article
    • research article
    • Vol. 38  (8) , 2233-2238
Abstract
The effect of the adenosine deaminase inhibitor, 2''-deoxycoformycin, on the inhibitory effect of cordycepin on nuclear RNA synthesis was examined in [mouse leukemia] L1210 cells in vitro. The median inhibitory dose for the effect of deoxycoformycin on adenosine deaminase was 4 .times. 10-8 M, and 100% inhibition was achieved at 5 .times. 10-7 M. Pretreatment of cells for 30 min with 1 .times. 10-6 M deoxycoformycin resulted in a reduction of the median inhibitory dose for cordycepin from 2.5 .times. 10-4 to 1.8 .times. 10-5 M, as assessed by the measurement of [3H]uridine incorporation into total RNA. Measurement of the synthesis of nuclear rRNA, non-poly(A) heterogeneous RNA and poly(A) heterogeneous RNA revealed potentiation by 2''-deoxycoformycin of the inhibitory effect of cordycepin on all species of RNA, as well as on poly(A) synthesis. No differences were noted in the size of nuclear poly(A) obtained from cells treated with cordycepin in the presence or the absence of the adenosine deaminase inhibitor. The potentiation by 2''-deoxycoformycin of the cytotoxic and antitumor effects of cordycepin on L1210 cells in vivo was related to inhibition of nuclear RNA synthesis.