Negative correlation of L-glutamine concentration with proliferation rate in rat hepatomas.

Negative correlation of L-glutamine concentration with proliferation rate in rat hepatomas.
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L-谷氨酰胺浓度与大鼠肝癌增殖率呈负相关。

DOI:
10.1016/0024-3205(84)90603-9
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发表时间:
1984
期刊:
影响因子:
6.1
通讯作者:
Weber,G
Weber,G
中科院分区:
医学2区
文献类型:
--
作者:
Sebolt,JS;Weber,G

文献摘要

被引文献

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测定了成年雄性喂养大鼠正常肝脏的冷冻样品(5.7-6.1 μmol /g)和增殖率差异很大的可移植肝癌中L-谷氨酰胺的浓度。L-谷氨酰胺浓度在缓慢生长的肝癌是在正常肝脏的范围内,它的肝癌生长速度的增加,在最快速生长的肿瘤相当于正常肝脏的12%的关系下降。在24小时再生肝中,谷氨酰胺含量略有降低(降低17%)。在正常大鼠的高细胞更新器官中,如睾丸、肠粘膜、脾和胸腺,L-谷氨酰胺浓度为正常大鼠肝脏的18 - 46%。L-谷氨酰胺含量在大鼠大脑和肝脏中相似,但在心脏中高出1.6倍,在血液中较低。谷氨酰胺合成酶(EC 6.3. 1.3)ACI/N品系大鼠正常成年肝脏中的活性为1,000 nmol/hr/mg蛋白质;在生长非常缓慢的肝癌20中活性增加,但在所有其他肝癌中显著降低。因此,谷氨酰胺合成酶活性基本上是转化相关的。谷氨酰胺含量与移植性肝癌生长速度的负相关性似乎与利用谷氨酰胺的酶的活性更密切相关。在快速生长的肝癌中,低L-谷氨酰胺浓度为选择性靶向谷氨酰胺利用酶的抗谷氨酰胺化疗提供了潜在的标志物。
The concentration of L-glutamine was determined in freeze-clamped samples of normal liver of adult male fed rats (5.7–6.1 μmol /g) and in transplantable hepatomas of vastly different proliferative rates. The L-glutamine concentration in the slowly growing hepatomas was in the range of the normal liver and it decreased in relation to the increase of hepatoma growth rate, in the most rapidly growing tumors amounting to 12% of that of normal liver. In 24-hour regenerating liver, the glutamine content was slightly reduced (by 17%). In normal rat organs of high cell renewal, such as testis, intestinal mucosa, spleen, and thymus, the L-glutamine concentration was 18 to 46% of that of normal rat liver. The L-glutamine content was similar in rat brain and liver, but it was 1.6-fold higher in the heart, and low in the blood. Glutamine synthetase (EC 6.3. 1.3) activity in normal adult liver of ACI/N strain rats was 1,000 nmol per hr per mg protein; the activity increased in the very slowly growing hepatoma 20, but decreased markedly in all the other hepatomas. Thus, glutamine synthetase activity was essentially transformation-linked. The negative correlation of glutamine content with growth rate in transplanted hepatomas appears to be more closely linked with the activities of enzymes that utilize glutamine. The low L-glutamine concentration in the rapidly growing hepatomas provides a potential marker for anti-glutamine chemotherapy selectively targeted against the glutamine-utilizing enzymes.