Related Experiment Videos
Two pathways for the induction of apoptosis in human lymphocytes
S P Cregan1, B P Smith, D L Brown
1Atomic Energy of Canada Ltd, Chalk River Laboratories, Ontario.
Purpose:
To assess the roles of cell membranes and DNA as targets in radiation-induced apoptosis.
Materials And Methods:
Peripheral blood lymphocytes from normal human donors were exposed to different types of apoptosis-inducing agents. Several measures of apoptosis were used to compare the kinetics of the processes induced, as well as to correlate the processes with DNA damage and membrane oxidation.
Results:
Two kinetically distinct processes were observed. DNA-damaging agents, such as ionizing radiation, bleomycin, cisplatin and the topoisomerase inhibitor m-amsacrine, induced apoptosis by a kinetically slow process initiated by DNA damage and dependent on protein synthesis, but which did not correlate with membrane oxidation. Conversely, the agents t-butyl hydroperoxide and cumene hydroperoxide induced apoptosis by a kinetically fast process independent of protein synthesis and which did correlate with membrane oxidation.
Conclusions:
Slowly repaired or unrepairable DNA lesions, such as some of those produced by ionizing radiation exposure, trigger apoptosis by a kinetically slow process. This slow apoptotic pathway is distinct from a fast process not induced by radiation but which is induced by membrane-oxidizing agents.