[13N]Ammonia and L-[amide-13N]glutamine metabolism in glutaminase-sensitive and glutaminase-resistant murine tumors.
[13N]Ammonia and L-[amide-13N]glutamine metabolism in glutaminase-sensitive and glutaminase-resistant murine tumors.
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谷氨酰胺酶敏感和谷氨酰胺酶抗性小鼠肿瘤中的[13N]氨和L-[酰胺-13N]谷氨酰胺代谢。
DOI：
10.1016/0304-4165(85)90047-9
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Roberts,J
中科院分区：
文献类型：
--
作者：
Rosenspire,KC;Gelbard,AS;Cooper,AJ;Schmid,FA;Roberts,J
在已知对谷氨酰胺酶治疗耐药（里奇韦成骨肉瘤（ROS））或敏感（肉瘤-180（S-180））的鼠肿瘤中，测定了来源于[13 N]氨或1-[酰胺-13 N]谷氨酰胺的标记氮的短期代谢命运。在腹膜内注射[13 N]氨或1-[酰胺-13 N]谷氨酰胺后5分钟，在两种肿瘤中仅回收约0.7%的标记物为蛋白质和核酸。[13 N]氨给药后，大部分标记物（超过80%）为代谢形式;大部分代谢标记物（50-57%）存在于尿素组分中，谷氨酰胺含量较低（37-42%）。源自l-[酰胺-13 N]谷氨酰胺的标记物的主要短期命运是掺入尿素循环的组分中，在酸性代谢物和酸性氨基酸中的量较小。在体外研究中，S-180肿瘤切片与[13 N]氨孵育期间未发现标记尿素，表明体内实验中肿瘤中形成的[13 N]尿素不是由于肿瘤中通过氨基甲酰磷酸从头合成所致。两种肿瘤均表现出极低的谷氨酰胺合成酶活性。谷氨酰胺酶治疗后，谷氨酰胺合成酶和γ-谷氨酰转移酶活性虽然保持较低水平，但在耐药肿瘤中增加，而在敏感肿瘤中不增加;这种增加可能与ROS肿瘤对谷氨酰胺酶治疗不敏感有关。
The short-term metabolic fate of labeled nitrogen derived from [13 N] ammonia or from l-[amide-13 N] glutamine was determined in murine tumors known to be resistant (Ridgeway Osteogenic Sarcoma (ROS)) or sensitive (Sarcoma-180 (S-180)) to glutaminase therapy. At 5 min after intraperitoneal injection of [13 N] ammonia or of l-[amide-13 N] glutamine, only about 0.7% of the label recovered in both tumors was in protein and nucleic acid. After [13 N] ammonia administration, most of the label (over 80%) was in a metabolized form; a large portion of this metabolized label (50–57%) was in the urea fraction with a smaller amount in glutamine (37–42%). The major short-term fate of label derived from l-[amide-13 N] glutamine was incorporation into components of the urea cycle with smaller amounts in the acidic metabolites and in acidic amino acids. No labeled urea was found during in vitro studies in which S-180 tumor slices were incubated with [13 N] ammonia, suggesting that the [13 N] urea formed in the tumor in the in vivo experiments was not due to de novo synthesis through carbamyl phosphate in the tumor. Both tumors exhibited very low glutamine synthetase activity. Following glutaminase treatment, glutamine synthetase and γ-glutamyltransferase activities, while remaining low, increased in the resistant tumor but not in the sensitive tumor; this increase may be related to the insensitivity of the ROS tumor toward glutaminase treatment.