Reactive intermediates and their toxicological significance.
Many chemicals that cause toxicity do so via metabolism to biologically reactive metabolites. However, the nature of the interaction between such reactive metabolites and various cellular components, and the mechanism(s) by which these interactions eventually lead to cell death are poorly understood. The relative importance of macromolecular alkylation (covalent binding), lipid peroxidation, alterations in thiol, calcium and energy homeostasis are discussed with reference to specific toxicants. It is concluded that the cytotoxic effects of reactive metabolites are a consequence of simultaneous and/or sequential alterations in several cellular processes. Further studies are required to determine the relationship between these alterations and cell death.
Monks
T J
TJ
University of Texas System Cancer Center, Science Park-Research Division, Smithville 78957.
Lau
S S
SS
D000082:Acetaminophen / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001711:Biotransformation; D001969:Bromobenzenes / Q000378:metabolism / Q000633:toxicity*; D002251:Carbon Tetrachloride / Q000378:metabolism / Q000633:toxicity*; D005965:Glucuronates / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D013431:Sulfates / Q000378:metabolism; D015262:Xenobiotics / Q000378:metabolism*
D001969:Bromobenzenes; D005965:Glucuronates; D013431:Sulfates; D015262:Xenobiotics; D000082:Acetaminophen; D002251:Carbon Tetrachloride; C032036:bromobenzene; D005978:Glutathione