Abstract

CCI4 has long served as a model compound for study of hepatotoxicity. While its simple chemical structure held the allure of a simple mechanism of action, decades of study have disclosed a complex series of responses. Significant early damage following CCI4 administration includes: (1) A number of alterations affecting Ca2+ homeostasis, which conspire to redistribute cellular Ca2+ from endoplasmic reticulum and mitochondria to cytosol, and (2) hypomethylation of ribosomal RNA, which disrupts protein synthesis. The genesis of the injury in vivo appears to encompass early 'metabolism-dependent' effects (which appear to be largely independent of CCI4 concentration at the levels studied) and later 'metabolism-independent' effects, which parallel CCI4 concentration. The inability of injured hepatocytes to respond anabolically to early damage may be a critical feature in CCI4 hepatotoxicity.

Original languageEnglish (US)
Pages (from-to)104-112
Number of pages9
JournalPathology and immunopathology research
Volume8
Issue number2
DOIs
StatePublished - Jan 1 1989

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Carbon Tetrachloride
Ribosomal RNA
Endoplasmic Reticulum
Cytosol
Hepatocytes
Mitochondria
Homeostasis
Wounds and Injuries
Proteins

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

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title = "Mechanisms of carbon tetrachloride hepatotoxicity.",
abstract = "CCI4 has long served as a model compound for study of hepatotoxicity. While its simple chemical structure held the allure of a simple mechanism of action, decades of study have disclosed a complex series of responses. Significant early damage following CCI4 administration includes: (1) A number of alterations affecting Ca2+ homeostasis, which conspire to redistribute cellular Ca2+ from endoplasmic reticulum and mitochondria to cytosol, and (2) hypomethylation of ribosomal RNA, which disrupts protein synthesis. The genesis of the injury in vivo appears to encompass early 'metabolism-dependent' effects (which appear to be largely independent of CCI4 concentration at the levels studied) and later 'metabolism-independent' effects, which parallel CCI4 concentration. The inability of injured hepatocytes to respond anabolically to early damage may be a critical feature in CCI4 hepatotoxicity.",
author = "Gary Clawson",
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}

Mechanisms of carbon tetrachloride hepatotoxicity. / Clawson, Gary.

In: Pathology and immunopathology research, Vol. 8, No. 2, 01.01.1989, p. 104-112.

Research output: Contribution to journalReview article

TY - JOUR

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AU - Clawson, Gary

PY - 1989/1/1

Y1 - 1989/1/1

N2 - CCI4 has long served as a model compound for study of hepatotoxicity. While its simple chemical structure held the allure of a simple mechanism of action, decades of study have disclosed a complex series of responses. Significant early damage following CCI4 administration includes: (1) A number of alterations affecting Ca2+ homeostasis, which conspire to redistribute cellular Ca2+ from endoplasmic reticulum and mitochondria to cytosol, and (2) hypomethylation of ribosomal RNA, which disrupts protein synthesis. The genesis of the injury in vivo appears to encompass early 'metabolism-dependent' effects (which appear to be largely independent of CCI4 concentration at the levels studied) and later 'metabolism-independent' effects, which parallel CCI4 concentration. The inability of injured hepatocytes to respond anabolically to early damage may be a critical feature in CCI4 hepatotoxicity.

AB - CCI4 has long served as a model compound for study of hepatotoxicity. While its simple chemical structure held the allure of a simple mechanism of action, decades of study have disclosed a complex series of responses. Significant early damage following CCI4 administration includes: (1) A number of alterations affecting Ca2+ homeostasis, which conspire to redistribute cellular Ca2+ from endoplasmic reticulum and mitochondria to cytosol, and (2) hypomethylation of ribosomal RNA, which disrupts protein synthesis. The genesis of the injury in vivo appears to encompass early 'metabolism-dependent' effects (which appear to be largely independent of CCI4 concentration at the levels studied) and later 'metabolism-independent' effects, which parallel CCI4 concentration. The inability of injured hepatocytes to respond anabolically to early damage may be a critical feature in CCI4 hepatotoxicity.

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