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1. |
Bioactivation of Halogenated Hydrocarbons by Cytochrome P4502E1 |
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Critical Reviews in Toxicology,
Volume 23,
Issue 1,
1993,
Page 1-20
RaucyJudy L,
KranerJames C.,
LaskerJerome M.,
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摘要:
AbstractNumerous halogenated hydrocarbons of the alkane, alkene, and alkyne classes are metabolized by P450 enzymes to products that elicit cytotoxic and/or carcinogenic effects. Such halogenated hydrocarbons include anesthetics (e.g., halothane andenflurane) and industrial solvents (e.g., carbon tetrachloride, chloroform, and vinylidine chloride). Formation of reaction intermediates from these compounds occurs via P450-promoted dehalogenation, reduction, or reductive oxygenation, with certain hydrocarbons undergoing all three reaction types. Of the multiple forms of P450 present in liver microsomes, P4502E1 has been identified as the primary catalyst of hydrocarbon bioactivation in animals and, most likely, in humans as well. As hepatic concentrations of this P450 enzyme are highly inducible by ethanol and similar agents, prior exposure to 2E1-inducing compounds can play a pivotal role in halogenated hydrocarbon toxicity. Considering that metabolism governs the cytotoxicity and carcinogenicity of halogenated hydrocarbons, an understanding of the mechanism(s) underlying 2E1 induction in man becomes all the more important.
ISSN:1040-8444
DOI:10.3109/10408449309104072
出版商:Taylor&Francis
年代:1993
数据来源: Taylor
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2. |
Free Radicals as Mediators of Tissue Injury and Disease |
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Critical Reviews in Toxicology,
Volume 23,
Issue 1,
1993,
Page 21-48
KehrerJames P.,
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摘要:
AbstractA radical is any molecule that contains one or more unpaired electrons. Radicals are normally generated in many metabolic pathways. Some of these radicals can exist in a free form and subsequently interact with various tissue components resulting in dysfunction. The potential role of oxygen- or xenobiotic-derived free radicals in the pathology of several human diseases has stimulated extensive research linking the toxicity of numerous xenobiotics and disease processes to a free radical mechanism. However, because free radical-mediated changes are pervasive and often poorly understood, the question of whether such species are a major cause of tissue injury and human disease remains equivocal. This review discusses cellular sources of various radical species and their reactions with vital cellular constituents. Examples of purported free radical-mediated disorders are discussed in detail to provide insights into the controversy over whether free radicals are important mediators of tissue injury.
ISSN:1040-8444
DOI:10.3109/10408449309104073
出版商:Taylor&Francis
年代:1993
数据来源: Taylor
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3. |
Stress Proteins in Aquatic Organisms: An Environmental Perspective |
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Critical Reviews in Toxicology,
Volume 23,
Issue 1,
1993,
Page 49-75
SandersBrenda M.,
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摘要:
AbstractThe cellular stress response protects organisms from damage resulting from exposure to a wide variety of stressors, including elevated temperatures, ultraviolet (UV) light, trace metals, and xenobiotics. The stress response entails the rapid synthesis of a suite of proteins referred to as stress proteins, or heat-shock proteins, upon exposure to adverse environmental conditions. These proteins are highly conserved and have been found in organisms as diverse as bacteria, molluscs, and humans. In this review, we discuss the stress response in aquatic organisms from an environmental perspective. Our current understanding of the cellular functions of stress proteins is examined within the context of their role in repair and protection from environmentally induced damage, acquired tolerance, and environmental adaptation. The tissue specificity of the response and its significance relative to target organ toxicity also are addressed. In addition, the usefulness of using the stress response as a diagnostic in environmental toxicology is evaluated. From the studies discussed in this review, it is apparent that stress proteins are involved in organismal adaption to both natural and anthropogenic environmental stress, and that further research using this focus will make important contributions to both environmental physiology and ecotoxicology.
ISSN:1040-8444
DOI:10.3109/10408449309104074
出版商:Taylor&Francis
年代:1993
数据来源: Taylor
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4. |
Toxicological and Pathological Applications of Proliferating Cell Nuclear Antigen (PCNA), A Novel Endogenous Marker for Cell Proliferation |
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Critical Reviews in Toxicology,
Volume 23,
Issue 1,
1993,
Page 77-109
DietrichDaniel R.,
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摘要:
AbstractA major stimulus to study cell proliferation, particularly in rodent carcinogenicity assays and human tumors, has been the belief that the quantification of this fundamental biological process will provide the toxicologist and pathologist with objective data allowing a better understanding of the mechanisms involved in the toxicity and/or carcinogenicity of certain compounds as well as guiding more effective management of patients afflicted with neoplasia. Among the markers used for cell proliferation measurement, PCNA has recently gained much attention and holds much promise as it is intricately involved in the cell replication processes. It not only could allow measurement of the replication rates without necessitating pretreatment of the animal/tissue in prospective studies, but also would allow retrospective assessment of the proliferative rates in archival tissues due to the conservation of this marker in fixed and paraffin-embedded tissues. Finally, knowledge of the function of PCNA in the cell cycle and its regulation by other factors may help us understand the advantages and limitations of PCNA as a cell proliferation marker in its application in toxicology and as a prognostic marker in human tumors.
ISSN:1040-8444
DOI:10.3109/10408449309104075
出版商:Taylor&Francis
年代:1993
数据来源: Taylor
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