脳腫瘍とCyclic Nucleotides （第1報）—各種脳腫瘍におけるcAMPとcGMP濃度

BRAIN TUMOR AND CYCLIC NUCLEOTIDES I. : CONCENTRATIOS OF CYCLIC AMP AND CYCLIC GMP IN VARIOUS BRAIN TUMORS

I．はじめに

　近年cyclic adenosine 3´，5´monophosphate （cAMP）およびcyclic guanosine 3´，5´monophosphate （cGMP）などのcyclic nucleotidesが細胞の分化や増殖に関係することが明らかにされてきた。

　cAMPは一般に細胞の分化を促進するが増殖を抑制し，一方cGMPはcAMPと逆に作用するという成績が報告され注目を集めている^{15,16,33,38）42）}。脳腫瘍に関しては，培養グリオーマ細胞がcAMPの存在下にある種の分化型へtransformすることが報告され^11,34,35）臨床的にも治療の手段の可能性が検討されている^24,47）。しかし脳腫瘍細胞の分化や増殖とcAMP，cGMPとの関連は明らかでなくまた脳腫瘍内のこれらcyclic nucleotidesの組織内濃度も詳細には検討されていない。

cAMP and cGMP have been reported to play important roles in differentiation and proliferation of cells. cAMP has also been shown to be impor-tant in the differentiation of cultured brain tumor cells. However, no precise ananlysis of cAMP and cGMP concentrations in brain tumor cells has yetbeen reported. The present studies were therefore undertaken to determine the concentration of cAMP and cGMP in brain tumors in reference to the histopathological findings.

Fifty fresh brain tumors and five brain specimen obtained during surgery were frozen instantly in liquid nitrogen. After homogenization and extrac-tion in ten times volume of 6% TCA, concentra-tion of cyclic nucleotides were determined by a specific and sensitive radioimmunoassy technique.

cAMP and cGMP concentrations in cerebral tissues were 1170±120 and 23.0±5.3 picomole/g wet weight respectively. Concentration of cAMP in glioma (16 cases) was one third that of control brain tissue, while glioblastoma with high cellu-larity and mitosis contained very low concentration of cAMP (130±34 picomole/g) but high concentra-tion of cGMP (59.9±35.7 picomole/g), resulting in a low ratio of cAMP/cGMP. This ratio was also very low in malignant meningioma (6.8) and malignant teratoma (9.1), while high ratios were observed in craniopharyngioma (167.1), benign meningioma (92.6) and hemangioblastoma (21.5). These results show that levels of cyclic nucleotides related to histological findings reveal the important critical function of cyclic nucleotides in the diffe-rentiation and proliferation of brain tumor cells.

Concentrations of cAMP and cGMP in CSF were also measured by the above radioimmunoassay method. Concentration of cAMP in CSF of brain tumor patients (17 cases) was 20.2±5. 1 picomole/ ml and that of controls (21 cases) was 5.6±1. 9 picomole/ml. High concentration of cAMP in CSF was observed in mengioma and neurinoma. Con-centration of cGMP in CSF of brain tumor patients was 9.9±2.1 picomole/ml and that of controls was 3.2±0.9 picomole/ml. High concentration of cGMP was observed in meningioma and glioma. The level of cyclic nucleotides in CSF might play an important role in screening for diagnosis of brain tumors.