Cell death in many different organisms requires the activation of proteolytic cascades involving cytosolic proteases. Here we describe a novel requirement in thymocyte cell death for the 20S proteasome, a highly conserved multicatalytic protease found in all eukaryotes. Specific inhibitors of proteasome function blocked cell death induced by ionizing radiation, glucocorticoids or phorbol ester. In addition to inhibiting apoptosis, these signals prevented the cleavage of poly(ADP‐ribose) polymerase that accompanies many cell deaths. Since overall rates of protein degradation were not altered significantly during cell death in thymocytes, these results suggest that the proteasome may either degrade regulatory protein(s) that normally inhibit the apoptotic pathway or may proteolytically activate protein(s) than promote cell death.

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Ethylene glycol ethers are common solvents. Some isomers are toxic for the reproduction and immunity functions of humans and laboratory animals and are antileukemic for rodents. The health hazards of ethylene glycol ethers may result from their ability to induce cell death in various organs or tissues. To study this possibility, the human leukemia cell lines HL-60, Molt3, and K562 were treated with ethylene glycol ethers. 2-Ethoxyethanol and 2-butoxyethanol were selected because they are among the most commonly used ethelyne glycol ethers, but little is known about their individual toxicity. Cell death was detected by trypan blue uptake, flow cytometry, DNA electrophoresis, and poly(ADP-ribose) polymerase proteolysis. The treatments lasted up to 72 h with doses ranging from 1 to 20 mM, which are high relative to the concentrations found in biological fluids of exposed workers. The highest dose of 2-butoxyethanol (20 mM) induced apoptosis in Molt3 cells after 72 h incubation. Other treatments had no effect, induced necrosis, or blocked the cells in the G1 phase of the cell cycle.

Ethylene glycol ethers are common solvents. Some isomers are toxic for the reproduction and immunity functions of humans and laboratory animals and are antileukemic for rodents. The health hazards of ethylene glycol ethers may result from their ability to induce cell death in various organs or tissues. To study this possibility, the human leukemia cell lines HL-60, Molt3, and K562 were treated with ethylene glycol ethers. 2-Ethoxyethanol and 2-butoxyethanol were selected because they are among the most commonly used ethelyne glycol ethers, but little is known about their individual toxicity. Cell death was detected by trypan blue uptake, flow cytometry, DNA electrophoresis, and poly(ADP-ribose) polymerase proteolysis. The treatments lasted up to 72 h with doses ranging from 1 to 20 mM, which are high relative to the concentrations found in biological fluids of exposed workers. The highest dose of 2-butoxyethanol (20 mM) induced apoptosis in Molt3 cells after 72 h incubation. Other treatments had no effect, induced necrosis, or blocked the cells in the G1 phase of the cell cycle.