INDUCTION OF APOPTOSIS BY BLEOMYCIN IN RESTING AND CYCLING HUMAN-LYMPHOCYTES

Bleomycin induces DNA and chromosome breakage, The differential sensit ivity to the drug has been used in vitro to identify individuals at hi gh risk of developing tumours, However, there are limited reports on t he ability of bleomycin to induce apoptosis, In this study we tested i nduction of apoptosis in human peripheral lymphocytes by bleomycin at different concentrations and different culture times using various par ameters, such as nuclear fragmentation and DNA fragmentation, evaluate d either in situ with terminal transferase and labelled nucleotides (T UNEL) or by flow cytometry analysis. We demonstrate that bleomycin ind uces apoptosis without previous permeabilization of the cell membrane, Cell death occurs mainly by apoptosis and not by necrosis, with signi ficant alteration of membrane lipoperoxidation (evaluated by luminesce nce).