The somatostatin analogue peptide TT-232 induces apoptosis and chromosome breakage in cultured human lymphocytes

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Abstract

Somatostatin receptors are supposed to be important in the regulation of apoptosis. In this study, we measured apoptosis occurring spontaneously, or induced by the synthetic somatostatin analogue, the peptide TT-232. We examined isolated human peripheral blood lymphocytes (PBL) from 32 nurses exposed bedside to cytostatic drugs, 12 chronic lymphoid leukaemia (CLL) patients prior to treatment, and 19 unexposed, healthy donors without anamnestic occupational exposure to genotoxic agents. Cells were stimulated by phytohaemagglutinin-P (PHA) and cultured for 69 h with or without 15 μg/ml TT-232, respectively. Cell kinetic parameters and apoptosis were determined by flow cytometry after staining with FITC-labeled anti-BrdU and propidium iodide (PI) and the results on spontaneous and peptide-induced apoptosis were compared with the obtained chromosome aberration frequencies (CA). The peptide TT-232 unexpectedly induced chromosome breakage in addition to apoptosis. The mean spontaneous apoptotic fractions were 6.65±0.89%, 6.46±0.53%, and 3.07±0.57%, and the mean CA yields in the samples without TT-232 were 1.74±0.46%, 2.44±0.40%, and 4.50±1.05%, for healthy subjects, nurses, and CLL patients, respectively. A total of 15 μg/ml TT-232 treatment in healthy subjects increased the mean CA frequency (10.38±1.57%), as well as the apoptotic cell fraction (2.63±0.45 times higher than the corresponding untreated sample). In TT-232-treated PBLs of nurses, CA remained unchanged and the mean apoptotic cell fraction showed only a slight increase (1.24±0.11 times higher than the untreated). Among CLL patients, TT-232 treatment significantly increased both CA (up to 17.83±4.04%) and the ratio of apoptotic cells (21.78±11.00 times higher than the untreated). These results demonstrated significant differences in apoptosis sensitivity in controls, nurses and CLL donors, after 15 μg/ml TT-232 treatment. Data also indicate that the induced CA yields in CLL donors with high CA are in correlation with TT-232-induced apoptosis. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)61-68
Number of pages8
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume465
Issue number1-2
DOIs
Publication statusPublished - febr. 16 2000

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ASJC Scopus subject areas

  • Genetics
  • Health, Toxicology and Mutagenesis

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