Morphological and molecular evidence of differentiation during etoposide-induced apoptosis in human lymphoblastoid cells

Abstract

The relationship between apoptosis and cell differentiation has been a subject for continuous debate, with evidence showing leukaemic cell differentiation and drug-induced apoptosis have reciprocal, interdependent and a highly schedule-dependent relationship. We have addressed this relationship in terms of a widely-used model for apoptosis induced by cytotoxic drugs: namely the effect of etoposide on CEM cells. In respect of commitment toward differentiation, we assessed changes in expression of marker genes and the level of CD3 antigenicity. Changes in these parameters following exposure of CEM cells to etoposide was similar to that observed following treatment of the same cells with phorbol 12-myristate 13-acetate (PMA), though this latter treatment did not cause cell death. Similarities in response to etoposide and PMA also included generation of 50 kilobase fragmentation of DNA and convolution of nuclei as assessed by transmission electron microscopy. However, condensation of chromatin and externalization of phosphatidylserine were only recorded in response to the cytotoxic drug and not in response to PMA. The data are consistent with apoptosis in these lymphoblastoid cells being accompanied by activation of specific markers of T-cell differentiation, but ultimately involving processes unequivocally associated with cell death. Cell Death and Differentiation (2000) 7, 548 ± 555.

Damage to nuclear DNA induced by Shiga toxin 1 and ricin in human endothelial cells1

“…3) (27,45,46). Indeed, DNA fragments Յ 50 Kb can be seen in HUVEC subjected to an apoptotic regimen (10 M etoposide for 30 min, followed by another 6 h in drug-free complete culture medium) included as a positive control (48). PACE analysis also reveals that treatment of HUVEC with the two toxins does not result in random generation of doublestranded DNA fragments, indicating that neither Stx1 nor ricin is able to produce DNA double-strand breaks.…”

Ultrastructure of retinal ganglion cell death after axotomy in chick embryos

“…This finding is not necessarily a sign of cell death and is frequently observed in normal healthy cells of many types, including neurons (Schwartzkroin and Kunkel, 1985;Monteiro et al, 1992) especially during development (LaVelle and Buschmann, 1983), but nuclear invaginations have in several cases been shown to result from axotomy (Barron et al, 1967;Hornung et al, 1989) and often occur in dying cells (Johnson et al, 2000;Ramirez et al, 2000), including neurons (Hornung et al, 1989;Sheen and Macklis, 1994). Other factors can also induce invaginations, including increased metabolic activity due to prolonged stimulation (Chan et al, 2000) or seizures (Pico and Gall, 1989).…”