Sakaguchi K, Tsujino M, Mizuno K, Hayano K, Ishida N
J Antibiot (Tokyo). 1975 Oct;28(10):798-803. doi: 10.7164/antibiotics.28.798.
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.
核苷类抗生素布累迪宁的苷元对L5178Y细胞的细胞毒性与布累迪宁一样强。苷元的细胞毒性特性与布累迪宁非常相似，二者的最低抑菌浓度均为10⁻⁵M。两种药物无论浓度如何，其生长抑制作用均可被鸟苷酸、鸟苷或鸟嘌呤逆转。然而，随着这些药物浓度的增加，鸟苷酸的逆转作用逐渐减弱，两种药物的剂量-反应曲线相似。两种药物均抑制胸苷和尿苷掺入L5178Y细胞的大分子中，但不抑制亮氨酸掺入，且它们的抑制作用均可被鸟苷酸逆转至相似程度。另一方面，苷元对L5178Y细胞的生长抑制作用仅被腺嘌呤阻止，而不被腺苷或腺苷酸阻止，而布累迪宁的作用则不被腺嘌呤阻止。这些结果表明，苷元本身并不抑制生长，但其作用是由于它被腺嘌呤磷酸核糖基转移酶等酶转化为布累迪宁所致。为使生长恢复，每摩尔苷元需要三摩尔腺嘌呤。当给大鼠口服苷元时，在它们的血清和尿液中可检测到布累迪宁。
