三尖杉酯类生物硷对小鼠白血病P388及L615蛋白质生物合成的影响

本文初步观察了四种三尖杉酯硷对³H-DL-亮氨酸、³H-L-门冬酰胺、¹⁴C-DL-苯丙氨酸掺入小鼠白血病P₃₈₈腹水细胞及L₆₁₅。脾组织蛋白质的作用。实验结果表明,在等毒性剂量(1/5 LD₅₀)下,一次腹腔(或静脉)给药,四种酯硷对P₃₈₈腹水细胞及L₆₁₅脾组织蛋白质生物合成抑制明显,作用较快,并具有相似的时间—反应曲线。一般在24小时基本恢复。

THE EFFECT OF HARRINGTONINE AND ITS ALLIED ALKALOIDS ON THE INCORPORATION OF LABELLED AMINO ACIDS INTO PROTEINS OF TRANSPLANTABLE LEUKEMIAS L-615 AND P-388 CELLS

The effects of harringtonine, homoharringtonine, isoharringtonine and deoxyharringtonine on the biosynthesis of proteins in leukemias L-615 and P-388 were studied.The results indicate that the inhibitory effects of harringtonine, homoharringtonine, isoharringtonine and deoxyharringtonine on the incorporation of radioactive labelled amino acids into proteins of the spleen of mice bearing transplantable leukemia L-615 and into protein of leukemia P-388 cells in vivo were very significant. When 1/5 of the LD₅₀ was injected into mice bearing leukemias L-615 and P-388 intraperitoneally or intravenously, respectively, the incorporation rates of ¹⁴C-DL-phenylanine or ³H-L-asparagine were reduced thirty minutes after single injection of the four alkaloids. Maximal inhibition was observed thirty minutes to 4 hours after drug administration and recovered after 24 hours. Generally the inhibitory effects of the four alkaloids was similar in terms of the time-effect curve. Even if 1/20 of LD₅₀ dose was used intraperitoneally, the inhibitory effect on ³H-DL-leucine incorporation by the four alkaloids in leukemia P-388 was still significant. It is very interestingthat harringtonine can not markedly influence the incorporation of ¹⁴C-DL-phenylalanine into the protein of the spleen of leukemic mice 24 hours after the last dose of five consecutive doses. It is suggested that the inhibitory effects of the four alkaloids on the incorporation of labelled amino acids into the protein of leukemic cells were significant, rapid and reversible.