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Morphological Differentiation of Cultured Mouse Glioblastoma Cells Induced by Dibutyryl Cyclic Adenosine Monophosphate¹

Department of Molecular Oncology, The Institute of Medical Science, The University of Tokyo, P. O. Takanawa, Tokyo [S. S., T. S.], and Department of Biochemistry, Chiba Cancer Research Institute, Nitona-cho, Chiba [K. Y., S. F.], Japan

A culture line of mouse glioblastoma cells changed morphologically to differentiated astrocyte-like cells when cultured in medium with dibutyryl cyclic adenosine monophosphate and theophylline. Morphological alteration occurred within only 5 hr when 3 mM dibutyryl cyclic adenosine monophosphate and 1 mM theophylline were used, and in 1 days when 1 mM dibutyryl cyclic adenosine monophosphate and 1 mM theophylline were used. Cells showing this morphological change reverted completely to immature cells when they were transferred to medium without these two chemicals. Addition of 1 or 3 mM dibutyryl cyclic guanosine monophosphate with 1 mM theophylline to the medium also induced development of cytoplasmic processes from these cells and the cells became stellate, although the cytoplasmic processes were not as long or as numerous as those induced by dibutyryl cyclic adenosine monophosphate, and the altered cells could not be referred to as differentiated glia cells. Sodium butyrate induced morphological alterations similar to those induced by dibutyryl cyclic guanosine monophosphate, but fewer cells showed these alterations.

Addition of cyclic adenosine monophosphate or cyclic guanosine monophosphate in the presence of theophylline or addition of theorphylline alone did not induce morphological changes of the cells.

¹ This work was supported by grants from the Ministry of Education and the Ministry of Health and Welfare, Japan, and from the Princess Takamatsu Cancer Research Fund.

Received 4/22/74. Accepted 6/ 3/75.