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Adv Exp Med Biol. 1991;283:699-705.

Extensive alteration of genomic DNA and rise in nuclear Ca2+ in vivo early after hepatotoxic acetaminophen overdose in mice.

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Toxicology Program, College of Pharmacy, University of New Mexico, Albuquerque 87131.


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.

[Indexed for MEDLINE]

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