N-(4-HYDROXYPHENYL)RETINAMIDE-INDUCED DEATH IN HUMAN LYMPHOBLASTOID-CELLS - 50 KB DNA BREAKAGE AS A MEANS OF DISTINGUISHING APOPTOSIS FROM NECROSIS

Experimental studies of N-(4-hydroxyphenyl)retinamide, a potential can cer chemopreventive agent, have primarily involved breast cancer and n euroblastoma cell populations together with an investigation of myeloi d leukemia cells and have principally been concerned with the inductio n of apoptosis. This investigation of N-(4-hydroxyphenyl)retinamide-in duced apoptosis using T-cell-derived human lymphoblastoid lines extend s these studies by indicating distinctive features associated with thi s drug. The induction of apoptosis is restricted to a limited concentr ation range, which, if exceeded, results in cell death by necrosis. Wh ile morphological changes typical of apoptosis induced by many agents are readily demonstrable after treatment of lymphoblastoid cells with 3 mu M N-(4-hydroxyphenyl)retinamide, distinctive features evident usi ng the retinoid include the absence of cell cycle arrest along with th e mode and pattern of DNA breakage. Analysis by conventional gel elect rophoresis indicated that internucleosomal fragmentation of DNA was an unreliable indicator of apoptosis. On the other hand, higher order DN A breakage was consistently detected during drug-induced apoptosis, bu t not as a result of treatment causing necrosis. (C) 1998 Elsevier Sci ence Ireland Ltd. All rights reserved.