Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1983-9-23
pubmed:abstractText
Most cases of chemical toxicity involve one or both of the fundamental pathological processes of "acute lethal injury" and "autoxidative cellular injury." The process of "acute lethal injury" by which toxic chemicals interfere with cellular energy metabolism, leading ultimately to cell death and tissue necrosis, is well known and reasonably understood. Inhibition of glycolysis, mitochondrial respiration, or oxidative phosphorylation, resulting in lack of ATP synthesis or inhibition of ATPase and other enzymes, leads to decreased efficiency of the sodium pump, hydropic degeneration, lipid accumulation, and eventually cell death. Less well known are the mechanisms whereby toxic chemicals initiate autoxidation, leading to "autoxidative cellular injury," disrupting cell membranes, and resulting in increased autophagocytosis, cell death, and mutations. Many reactive intermediates of toxic chemicals are electrophiles, free radicals, or free-radical generators, which may potentiate the toxicity of tissue oxygen, depleting intracellular glutathione and biological antioxidants, resulting in membrane damage, impairment of the calcium pump, cell death, and damage to DNA. The mechanisms of oxygen toxicity and chemical-mediated oxygen toxicity are discussed, with particular reference to the microsomal mixed-function oxidase system and its role in the detoxication and activation of environmental chemicals. The dependence of tissue oxygen concentration, the rates of oxidative activation of chemicals, and the extents of autoxidative cellular injury on the size of the animal species is considered, and the importance of this to the scientific evaluation of chemical toxicity is discussed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0273-2300
pubmed:author
pubmed:issnType
Print
pubmed:volume
2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
267-86
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1982
pubmed:articleTitle
Mechanisms of chemical toxicity--a unifying hypothesis.
pubmed:publicationType
Journal Article