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APOPTOSIS INDUCTION IN HUMAN MALIGNANT LYMPHOID CELLS BY DNA-DAMAGING AGENTS WITH DIFFERENT MECHANISMS OF ACTION
Induction of apoptosis by fludarabine phosphate and etoposide in human malignant lymphoid cell lines Namalwa, Raji, CEM, and MT-4 was analyzed on comparative basis using morphological criteria, flow cytometry and DNA electrophoresis in agarose gel. B cell line Namalwa was shown to be less susceptible to etoposide than to fludarabine. At the same time B cell line Namalwa was more resistant to etoposide than T cell line CEM. Fludarabine induced apoptosis both in B and T (MT-4) cells. While etoposide induced apoptosis in 4 h upon the beginning of incubation (short-term apoptosis), specific apoptotic changes induced by fludarabine were evident only in 72 h (delayed apoptosis). Preincubation of Namalwa or MT-4 cells with non-toxic concentration of zinc sulfate (40 mol/l) makes them more susceptible to apoptosis induction by etoposide and not by fludarabine being suggestive of zinc potentiation of short-term apoptosis in malignant lymphoid cells under study.
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