Biochemical mechanisms of induction of hepatic peroxisome proliferation

EA Lock, AM Mitchell… - Annual Review of …, 1989 - annualreviews.org
EA Lock, AM Mitchell, CR Elcombe
Annual Review of Pharmacology and Toxicology, 1989annualreviews.org
The process of xenobiotic-induced proliferation of the cytoplasmic organelle, the
peroxisome, in mammalian liver cells has received considerable attention because of the
proposed relationship between the induction of hydrogen peroxide producing peroxisomal
enzymes and the development of hepa tocellular carcinomas in mice and rats (1-6). Several
structurally dissimilar hypolipidemic drugs, certain phthalate esters used as plasticizers, and
some halogenated hydrocarbon solvents are examples of important categories of chemicals …
The process of xenobiotic-induced proliferation of the cytoplasmic organelle, the peroxisome, in mammalian liver cells has received considerable attention because of the proposed relationship between the induction of hydrogen peroxide producing peroxisomal enzymes and the development of hepa tocellular carcinomas in mice and rats (1-6). Several structurally dissimilar hypolipidemic drugs, certain phthalate esters used as plasticizers, and some halogenated hydrocarbon solvents are examples of important categories of chemicals that are capable of inducing proliferation of peroxisomes in hepato cytes (7-13).
The mechanism by which this diverse group of chemicals causes peroxi some. proliferation and liver tumors is not understood, although it is currently thought that these chemicals are carcinogenic because of their ability to induce peroxisome proliferation. There are marked species diffcrcnces in response to them; certain species, eg guinea pigs and monkeys, are relative ly nonresponsive or resistant to the induction of hepatic peroxisomes (l, 2, 4, 6). It is therefore necessary to understand the mechanism by which they induce peroxisome proliferation to help in the safety evaluation of these chemicals to human beings.
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