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Several mechanisms have been proposed, including effects on plasma membrane Ca 2 + pumps (Tsokos-Kuhn, 1989), which can lead to Ca 2 + -induced DNA damage (Ray et al ., 1990), mito-chondrial damage (Meyers et al ., 1988) resulting in glutathione depletion and oxidative stress (Jaeschke, 1990) and apoptosis (Ray et al ., 1996)