Effect of bredinin and its aglycone on L5178Y cells

  • Sakaguchi K
  • Tsujino M
  • Mizuno K
 et al. 
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Abstract

The aglycone of the nucleoside antibiotic, bredinin, was as strongly cytotoxic to L5178Y cells as bredinin. The cytotoxic properties of the aglycone were very similar to those of bredinin and the minimum inhibitory concentrations of both were 10(-5)M. The growth inhibitory effects of both agents regardless of their concentrations, were reversed by guanylic acid, guanosine or guanine. However, on increasing the concentrations of these agents, the reversing effect of guanylic acid decreased gradually, the dose-response curves for the two agents being similar. Both agents inhibited the incorporation of thymidine and uridine, but not leucine into macromolecules in L5178Y cells and their inhibitory effects were reversed to similar extents by guanylic acid. On the other hand, the growth inhibitory effect of the aglycone on L5178Y cells was prevented by adenine only, though not be adenosine or adenylic acid while the effect of bredinin was not prevented by adenine. These results suggest that the aglycone itself does not inhibit growth, but that its effect is due to its conversion to bredinin by an enzyme such as adenine phosphoribosyl transferase. For recovery of growth, three moles of adenine were required per mole of the aglycone. When the aglycone was administered orally to rats, bredinin was administered orally to rats, bredinin was recovered in their serum and urine.

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Authors

  • Kengo Sakaguchi

  • Masatoshi Tsujino

  • Kimio Mizuno

  • Kazuo Hayano

  • Nakao Ishida

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