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Mutat Res. 2000 Feb 16;465(1-2):61-8.The somatostatin analogue peptide TT-232 induces apoptosis and chromosome breakage incultured human lymphocytes.Tompa A, Jakab MG, Major J, Idei M, Bocsi J, Mihalik R, Szende B, Keri G.Somatostatin receptors are supposed to be important in the regulation of apoptosis. In thisstudy, we measured apoptosis occurring spontaneously, or induced by the syntheticsomatostatin analogue, the peptide TT-232. We examined isolated human peripheralblood lymphocytes (PBL) from 32 nurses exposed bedside to cytostatic drugs, 12chronic lymphoid leukaemia (CLL) patients prior to treatment, and 19 unexposed,healthy donors without anamnestic occupational exposure to genotoxic agents. Cellswere stimulated by phytohaemagglutinin-P (PHA) and cultured for 69 h with or without15 microg/ml TT-232, respectively. Cell kinetic parameters and apoptosis weredetermined by flow cytometry after staining with FITC-labeled anti-BrdU and propidiumiodide (PI) and the results on spontaneous and peptide-induced apoptosis werecompared with the obtained chromosome aberration frequencies (CA). The peptide TT-232 unexpectedly induced chromosome breakage in addition to apoptosis. The meanspontaneous 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 microg/ml TT-232 treatment in healthy subjects increasedthe 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 fractionshowed only a slight increase (1.24+/-0.11 times higher than the untreated). AmongCLL 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). Theseresults demonstrated significant differences in apoptosis sensitivity in controls, nursesand CLL donors, after 15 microg/ml TT-232 treatment. Data also indicate that theinduced CA yields in CLL donors with high CA are in correlation with TT-232-inducedapoptosis.
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