Broome J D
J Exp Med. 1968 Jun 1;127(6):1055-72. doi: 10.1084/jem.127.6.1055.
L-asparaginases of agouti serum and Escherichia coli cause a profound lowering in the level of free asparagine in the blood of treated mice and also in the tissues. During treatment, normal tissues and resistant 6C3HED lymphomas survive unharmed with intracellular asparagine levels which are critically low for sensitive lymphomas. An explanation for this contrast between the two types of lymphoma is provided by the finding that resistant cells have not only a higher asparagine synthetic capacity than sensitive cells but appear able to utilize endogenous asparagine preferentially for protein synthesis. Cell-free extracts of resistant cells contain an asparaginase synthetase, but this is not found in preparations from sensitive cells.
刺豚鼠血清和大肠杆菌的L-天冬酰胺酶会使接受治疗的小鼠血液及组织中的游离天冬酰胺水平大幅降低。在治疗过程中,正常组织和耐药的6C3HED淋巴瘤能够安然无恙地存活,其细胞内天冬酰胺水平对于敏感淋巴瘤来说极低。两种类型淋巴瘤之间这种差异的一种解释是,研究发现耐药细胞不仅比敏感细胞具有更高的天冬酰胺合成能力,而且似乎能够优先利用内源性天冬酰胺进行蛋白质合成。耐药细胞的无细胞提取物含有天冬酰胺酶合成酶,但在敏感细胞的提取物中未发现这种酶。