Keefer J F, Moraga D A, Schuster S M
Biochem Med. 1985 Oct;34(2):135-50. doi: 10.1016/0006-2944(85)90105-x.
The amino acid contents of tumor cells that are either sensitive or resistant to treatment with L-asparaginase were measured. These amino acid concentrations were measured as a function of incubation time with L-asparaginase or as a function of the L-asparaginase dose. The cell types compared were the mouse leukemia lines L5178Y (sensitive to L-asparaginase treatment) and L5178Y/L-ASE (resistant to L-asparaginase treatment). Upon L-asparaginase treatment both cell lines lost most of their cellular asparagine but, whereas the resistant cells exhibited the ability to rebound to about 50% of initial values, the sensitive cells did not. While previous work had suggested that asparagine-dependent glycine synthesis was essential for sensitive cells (but not in resistant cells), we found no difference in the glycine content of either of the two cell lines as a function of either time or dose that would support this hypothesis. Major differences between the two cell lines were seen in the content of the essential amino acids before treatment with L-asparaginase. After incubation without L-asparaginase the contents of the two cell lines became similar. These results are discussed in terms of possible mechanisms of L-asparaginase sensitivity and resistance.
对用L-天冬酰胺酶治疗敏感或耐药的肿瘤细胞的氨基酸含量进行了测定。这些氨基酸浓度是作为与L-天冬酰胺酶孵育时间的函数或作为L-天冬酰胺酶剂量的函数来测量的。所比较的细胞类型是小鼠白血病细胞系L5178Y（对L-天冬酰胺酶治疗敏感）和L5178Y/L-ASE（对L-天冬酰胺酶治疗耐药）。经L-天冬酰胺酶处理后，两种细胞系的细胞内天冬酰胺大部分都丢失了，但是，耐药细胞表现出能反弹至初始值约50%的能力，而敏感细胞则不能。虽然先前的研究表明天冬酰胺依赖性甘氨酸合成对敏感细胞至关重要（但对耐药细胞并非如此），但我们发现两种细胞系中任一种的甘氨酸含量作为时间或剂量的函数均无差异，无法支持这一假设。在用L-天冬酰胺酶处理之前，两种细胞系在必需氨基酸含量上存在主要差异。在不添加L-天冬酰胺酶的情况下孵育后，两种细胞系的含量变得相似。从L-天冬酰胺酶敏感性和耐药性的可能机制方面对这些结果进行了讨论。
