Bardot V, Dutrillaux A M, Reillaudou M, Dutrillaux B, Luccioni C
DSV/DPTE/LCG CEA, Fontenay-aux-Roses, France.
Bull Cancer. 1994 Apr;81(4):297-302.
A study developed to test the hypothesis of a possible relationship between metabolic modifications and chromosomal imbalances in solid tumors leads us to investigate the metabolism of purine nucleotides in human gliomas. In order to assess the representativeness of experimental models frequently used, the activities of nine enzymes involved in the synthesis and in the catabolism of purine nucleotides were measured on samples of normal brain, primary and xenografted glial tumors and cell cultures established from human gliomas. In parallel, two enzymes involved in pyrimidine metabolism were also studied on the same samples. The results highlight the low activity of the purine metabolism in human gliomas when compared to normal brain, tissue with low proliferative activity. On the contrary, the pyrimidine metabolism in human gliomas is increased by comparison to normal brain. For the purine metabolism, few differences are observed between enzyme activities calculated in primary glial tumors, xenografts and cells in culture. In grafted tumors and cell cultures, the activity of this metabolism is similar or lower than in normal brain, except for inosine monophosphate dehydrogenase. However, for the pyrimidine metabolism, significantly differences are observed between primary glial tumors, grafted glial tumors and cell cultures. The thymidine kinase/thymidylate synthetase ratio depends on the model studied. These results point out the problem of the representativeness of these models, especially when used for experimental therapeutic studies. This metabolic study also underlines that all results should be interpreted carefully and that the limits for the use of these two experimental models should always be clearly exposed.
一项旨在检验实体瘤中代谢改变与染色体失衡之间可能存在的关系这一假设的研究，引导我们对人类神经胶质瘤中嘌呤核苷酸的代谢进行研究。为了评估常用实验模型的代表性，我们测定了正常脑样本、原发性和异种移植神经胶质瘤样本以及从人类神经胶质瘤建立的细胞培养物中参与嘌呤核苷酸合成和分解代谢的九种酶的活性。同时，我们还对同一样本中参与嘧啶代谢的两种酶进行了研究。结果表明，与正常脑相比，人类神经胶质瘤中嘌呤代谢的活性较低，而正常脑是增殖活性较低的组织。相反，与正常脑相比，人类神经胶质瘤中的嘧啶代谢有所增加。对于嘌呤代谢，在原发性神经胶质瘤、异种移植瘤和培养细胞中计算出的酶活性之间几乎没有差异。在移植瘤和细胞培养物中，除了肌苷单磷酸脱氢酶外，这种代谢的活性与正常脑相似或更低。然而，对于嘧啶代谢，在原发性神经胶质瘤、移植神经胶质瘤和细胞培养物之间观察到显著差异。胸苷激酶/胸苷酸合成酶的比值取决于所研究的模型。这些结果指出了这些模型代表性的问题，尤其是在用于实验性治疗研究时。这项代谢研究还强调，所有结果都应谨慎解释，并且这两种实验模型的使用限制应始终明确说明。
