Biochemical Changes in Experimental Rat Brain Tumors Induced by Ethylnitrosourea and Human Gliomas after Dibutyryl Cyclic AMP Treatment

• Published in: Neurologia medico-chirurgica Vol. 22; no. 1; pp. 1 - 6
• Main Authors: SHIBATA, Iekado, MATSUMOTO, Mikiro, NAGASAWA, Sadatsugu, SEIKI, Yoshikatsu, TAKEZAWA, Junichi
• Format: Journal Article
• Language: English
• Published: Japan The Japan Neurosurgical Society 1982; THE JAPAN NEUROSURGICAL SOCIETY
• Subjects: Animals; Antineoplastic Agents; Brain Neoplasms - drug therapy; Bucladesine - therapeutic use; cyclic AMP; dibutyryl 3', 5'-adenosine monophosphate (DBc-AMP); experimental brain tumor; free amino acids; Glioma - drug therapy; Humans; lysosomal enzyme; Neoplasms, Experimental - drug therapy; nucleic acids; Rats
• ISSN: 0470-8105; 1349-8029
• DOI: 10.2176/nmc.22.1

Previous reports have shown that dibutyryl 3', 5'adenosine monophosphate (DBc-AMP) suppresses growth of actively dividing tumor cells, accelerates normalization of cellular metabolism and elevates the intracellular level of cyclic AMP. In an effort to study this mechanism further and define its significance, studies were performed on pregnant rats with ethylnitrosourea (ENU) induced gliomas and human subjects with malignant gliomas. RNA and DNA were detected in remarkably high concentrations in the tumor tissue with a significant reduction after treatment with DBc-AMP. The reduction was more pronounced with RNA. Free amino acids were noted in relatively low concentrations in tumor tissue. However, treatment with DBc-AMP resulted in a significant elevation of their value. The levels of glutamic acid, aspartic acid and GABA increased to levels corresponding to the composition of free amino acids in normal brain tissues. Lysosomal enzyme activity in tumor tissue was 10 times greater than that in normal brain tissue. This activity dropped significantly after administration of DBc-AMP. In rats with ENU induced glioma, the uptake of radiocative [H3] DBc-AMP by tumor tissue occurred in a volume 2-3 times that of normal tissue. However, the ratio of [H3] cyclic AMP/cyclic AMP was less than that in normal tissue, implying that an enhanced synthesis of endogenous cyclic AMP occurs after administration of DBc-AMP.