Apoptosis and cytotoxins

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Most xenobiotics ultimately become lethally cytotoxic, according to concentration. Toxins with completely disparate mechanisms of action induce apoptotic cell death. This suggests that the threshold for the onset of cell death can be determined by the relative expression levels of genes which promote or suppress apoptosis. The selectivity of a toxin may thus be determined not only by the selective imposition of perturbation or the amount of damage inflicted, but also by how readily that cell engages apoptosis. Measuring damage to cells, therefore, does not necessarily predict outcome. The threshold for apoptosis is determined not only by the static phenotype of the cell, which may confer a high or low survival potential, but also by its capability when stressed to modulate the expression of genes which control survival. The trophic environment of a cell can also influence the threshold for death. These findings have a profound impact on concepts defining toxin selectivity and on attempts to use mechanistic information to predict toxicity to organisms.

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