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Free-Radical-Mediated Alterations of Gene Expression by Xenobiotics.

Authors
Timblin-CR; Janssen-YM; Mossman-BT
Source
Free Radical Toxicology 1997:325-348
Link
NIOSHTIC No.
00241819
Abstract
A review of free radical mediated alterations of gene expression by xenobiotics was presented. Possible mechanisms by which xenobiotic agents can induce gene expression through free radical formation were summarized. A number of toxic xenobiotic agents have been shown to induce formation of free radicals either spontaneously, through metabolic pathways, or by interacting with cells. Cellular production of free radicals by xenobiotics may occur as a result of a direct interaction with cellular macromolecules or indirectly through a mechanism that involves a number of signaling cascades. At low levels of xenobiotic exposure, harmful free radical reactions may be suppressed by the antioxidant defenses of target cells or cells in the immune system. Extracellular fluids such as serum, blood, and lavage fluids also contain a number of naturally occurring antioxidants, such as ceruloplasmin, ascorbic-acid, or superoxide-dismutase, that can quench free radical reactions before they affect cells. When the ratio of oxidative stress begins to disproportionately exceed a cell's antioxidant status, alterations in gene expression that can result in disease develop. Specific examples of agents that can induce pathological processes attributed to free radical mediated gene expression were described. These include cadmium (7440439), nickel (7440020), chromium (7440473), tobacco smoke, 2,3,7,8-tetrachlorodibenzo-p-dioxin (1746016), ozone (10028156) and other oxidant gases, asbestos (1332214), and crystalline silica (14808607). The authors conclude that elucidating the processes by which oxidants induce their toxic effects is key to understanding the pathogenesis of disease and developing effective therapeutic approaches.
Keywords
NIOSH-Grant; Cancer; Free-radicals; Genetics; Oxidative-processes; Cell-function; Physiological-stress; Host-resistance; Toxic-effects;
Contact
Pathology University of Vermont Medical Alumni Bldg Burlington, VT 05405
CAS No.
7440-43-9; 7440-02-0; 7440-47-3; 1746-01-6; 10028-15-6; 1332-21-4; 14808-60-7;
Publication Date
19970101
Document Type
Book or book chapter;
Editors
Wallace-KB;
Funding Amount
162000.00
Funding Type
Grant;
Fiscal Year
1997
NTIS Accession No.
NTIS Price
ISBN No.
1560326328
Identifying No.
Grant-Number-K01-OH-000146
Source Name
Free Radical Toxicology
State
NY; VT;
Performing Organization
University of Vermont & St Agric College, Burlington, Vermont
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