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Characterisation of the toxic metabolite(s) of naphthalene.
The data suggests that the cytotoxicity and genotoxicity of naphthalene is associated with the formation of quinones from 1-naphthol rather than nAPHthalene-1,2-epoxide. Expand
Relationship of cytochrome P-450 activity to Clara cell cytotoxicity. I. Histopathologic comparison of the respiratory tract of mice, rats and hamsters after parenteral administration of naphthalene.
The sites of cytotoxicity within the respiratory tract (nasal cavity and tracheobronchial airway tree) resulting from administration of naphthalene, an organic chemical whose cytotoxic properties require metabolic activation via the cytochrome P-450 monooxygenase system were defined. Expand
It is argued that a complete understanding of the cellular and biochemical mechanisms by which this and other lung toxic compounds generate their effects in rodent models with subsequent measurement of these Cellular and biochemical events in primate and human tissues in vitro will provide a far better basis for judging whether the results of studies done in rodent model studies are applicable to humans. Expand
Cellular response in naphthalene-induced Clara cell injury and bronchiolar epithelial repair in mice.
Clara cells, progenitors for bronchiolar epithelium, are also primary targets for metabolically activated pulmonary cytotoxicants and have an abundance of the cytochrome P-450 monooxygenases requiredExpand
Role of murine cytochrome P-450 2F2 in metabolic activation of naphthalene and metabolism of other xenobiotics.
It is suggested that CYP2F2 plays a key role in the species- and cell-selective toxicity of naphthalene and efficiently metabolizes a number of other substrates, including the lung toxicant 1-nitronaphthalenes. Expand
Evidence for cytochrome P-450 mediated metabolism in the bronchiolar damage by naphthalene.
The view that naphthalene-induced pulmonary damage is mediated by the cytochrome P-450-dependent metabolism of naphhalene and that glutathione plays an important role in the detoxification of the lung damaging metabolite(s) is supported. Expand
Relationship of cytochrome P450 activity to Clara cell cytotoxicity. II. Comparison of stereoselectivity of naphthalene epoxidation in lung and nasal mucosa of mouse, hamster, rat and rhesus monkey.
Analysis of the three diasteriomeric glutathione adducts produced from conjugation of naphthalene oxides was used in these studies to characterize the stereochemistry of nphthalene epoxidation in preparations of nasal mucosa, lung and liver of the mouse, rat, hamster and monkey. Expand
Metabolism and cytotoxicity of naphthalene and its metabolites in isolated murine Clara cells.
It is concluded that isolated Clara cells are capable of metabolizing naphthalene, a Clara cell-specific cytotoxicant, to two major metabolites, have a detectable intracellular glutathione pool, and are more susceptible to specific naphhalene metabolites than to the parent compound nphthalene. Expand
Glutathione depletion is a major determinant of inhaled naphthalene respiratory toxicity and naphthalene metabolism in mice.
GSH depletion occurs in airways independent of hepatic function, sufficient GSH is not supplied by the liver to maintain respiratory GSH pools, or to prevent injury from inhaled naphthalene, and GSH loss precedes injury and increases protein adduct formation. Expand
Unique gene expression patterns in liver and kidney associated with exposure to chemical toxicants.
Comparison of changes in messenger RNA expression between the kidney and liver of treated animals indicates that gene arrays may be useful in determining the comparative toxicity of chemicals in various tissues but that exposure to uncharacterized chemicals will have to be monitored in several tissues. Expand