EFFECT OF 5'-METHYLTHIOADENOSINE AND ITS ANALOGS ON MURINE LYMPHOID-CELL PROLIFERATION

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (8) , 3035-3039
Abstract
The effect of 5''-deoxy-5''-methylthioadenosine (MTA) on the growth of culture murine lymphoid cells was examined. MTA inhibited the growth of murine lymphoid cell lines of both B-cell [BW 5147] and T-cell [NS-1] origin in a reversible, nontoxic and dose-dependent fashion. When measured 2 days after the addition of MTA to the cells, the concentration that inhibited proliferation by 50% for MTA was .apprx. 250 .mu.M. Cells incubated in the presence of 0.5 mM MTA for 1, 2 or 3 days were able to recover from the inhibitory effect of the nucleoside and resumed growth. Six structural analogs of MTA inhibited cell growth. Five of these analogs served as alternative substrates for MTA phosphorylase, while one, the 7-deaza analog (5''-deoxy-5''-methylthiotubercidin), was not a substrate for the phosphorylase but was a potent inhibitor of enzyme activity. Inhibition of growth by 5''-deoxy-5''-methylthiotubercidin was dose dependent (the concentration that inhibited proliferation by 50% .simeq. 10 .mu.M) and at 50 .mu.M was reversible and nontoxic.