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Extensive Alteration Of Genomic DNA And Rise In Nuclear Ca2+ In Vivo Early After Hepatotoxic Acetaminophen Overdose In Mice.

S. Ray, C. L. Sorge, A. Tavacoli, J. Raucy, G. Corcoran
Published 1991 · Biology, Medicine

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Hepatotoxic doses of acetaminophen cause early impairment of Ca2+ homeostasis. In this in vivo study, 600 mg/kg acetaminophen caused total nuclear Ca2+ and % fragmented DNA to rise in parallel from 2-6 hr, followed by large later increases mirroring frank liver injury. Agarose gel electrophoresis revealed substantial loss of large genomic DNA from 2 hours onward, with accumulation of DNA fragments in a ladder-like pattern resembling apoptosis. Extensive late cleavage of DNA probably resulted from cell death, whereas degradative loss of large genomic DNA at 2 hours arose at an early enough point to contribute to acetaminophen-induced liver necrosis in mice.
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