Cyclic nucleotides in experimental and human brain tumors.

It is well known that the system of cyclic nucleotides plays an important role in cell differentiation and proliferation. Cyclic AMP is capable of stimulating cell growth, and cyclic GMP is thought to control cell division and growth. The authors measured adenylcyclase activity (AC) and cGMP content in the tumor latency period and in early neoplastic proliferations in rats with brain tumors induced by transplacental ethylnitrosourea (ENU). AC activity, which is high during the first days of life, decreases until it reaches, at the 60th day, levels lower than those in control animals. Cyclic GMP, on the contrary, increases during the first month in treated animals and remains consistently higher than controls up to the 45th day. In fully developed experimental brain tumors (mixed gliomas, isomorphic and polymorphic oligodendrogliomas) the percentage of reduction in AC activity is significantly higher. AC activity was measured also in human tumoral tissue. In malignant tumors it is markedly lower than in benign tumors. In the same patients cAMP in the cerebrospinal fluid was measured with results similar to those obtained in tissues. These findings confirm that the system of cyclic nucleotides is implicated in all the developmental phases of brain tumors and therefore may reveal how research can clarify the first transformations of tumoral cells.