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aDepartment of Medical Biochemistry, b2nd Department of Internal Medicine, cDepartment of Neurosurgery, dDepartment of Medical Biology and Genetics, Charles University in Prague, Faculty of Medicine in Hradec Kralove, 500 38 Hradec Kralove, Czech Republic e3rd Department of Internal Medicine in Prague, Charles University in Prague, Prague, Czech Republic
Address for correspondence: Jaroslav Cerman, Department of Medical Biochemistry, Charles University in Prague, Faculty of Medicine in Hradec Kralove, P.O. Box 38, 500 38 Hradec Kralove, Czech Republic. Voice: +420-495816222; fax: +420-495513597. cerman{at}lfhk.cuni.cz Ann. N.Y. Acad. Sci. 1010: 520-524 (2003).
The aim of the study was to investigate the mechanism of action of somatostatin analogues (SSA), ionizing radiation, and their combination on pituitary adenoma cells with special emphasis on proliferative and apoptotic activity. In the 14 GH-secreting adenomas pretreated with SSA before surgery, more prominent regressive changes were found accompanied by compensatory increase in perivascular fibrosis than in the reference group of 17 unpretreated adenomas. The proliferative Ki-67 labeling index was significantly lower in the treated group (median 1.6 per 1000) than in the untreated patients (median 5.0 per 1000). Apoptosis was detected in only 2 of the 14 pretreated adenomas, and it was more frequent (9/17) and more prominent in the untreated group. In cell lines, the SSA had minimal antiproliferative effect, and they were unable to induce apoptosis. Ionizing radiation at doses of 5-20 Gy induced apoptosis in the corticotroph cell line AtT20 with no cell-cycle block. In the somatotroph GH3 cell line, the early (premitotic) apoptosis was detectable using only a high dose of 200 Gy; after irradiation with doses of 20-50 Gy, apoptosis appeared with the latency of 48-72 hours, and was preceded by cell-cycle arrest in the G2/M phase. The treatment with somatostatin-14 during irradiation increased the percentage of apoptotic cells in culture 10 days after irradiation (11% versus 3% using 20 Gy).
Key Words: apoptosis • pituitary adenomas • acromegaly • somatostatin analogues • irradiation • cell lines
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