Sites for xenobiotic activation and detoxication within the respiratory tract: Implications for chemically induced toxicity

Baron, Jeffrey; Burke, Jon P.; Guengerich, F. Peter; Jakoby, William B.; Voigt, Jeffrey M.

doi:10.1016/0041-008x(88)90053-1

Cited by 59 publications

(26 citation statements)

References 39 publications

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“…In all studies the antibody has been raised against purified rat hepatic cytochrome P-450 and, therefore, recognizes antigens in nasal mucosa of immunochemical similarity to those in liver. The phenobarbital-inducible isozyme of cytochrome P-450 and NADPH-cytochrome P-450 reductase and the P-naphthoflavone-inducible form of P-450 have been studied (52)(53)(54). The pattern of enzyme distribution for both P-450 isozymes is similar to that for NBE and parallels the distribution of covalently bound radiolabeled compounds known to be metabolized to reactive products by cytochrome P-450.…”

Section: Metabolism Of P-450 Substratesmentioning

confidence: 84%

“…Two other enzymes related to metabolic activation and detoxication of chemicals, epoxide hydrolase (EH) and glutathione S-transferase (GSHt), have also been localized immunocytochemically (53). Epoxide hydrolase catalyzes the hydration of electrophilic epoxide moieties to vicinal diols in alkene and arene molecules.…”

Section: Metabolism Of P-450 Substratesmentioning

confidence: 99%

“…Similar to NBE, basal cells of the olfactory epithelium stain negatively for P-450. The distribution of benzo(a)pyrene hydroxylase (BaPOH), a cytochrome P-450-dependent monooxygenase catalyzing the hydroxylation of the polycyclic aromatic carcinogen benzo(a)pyrene, corresponds with that of P-450 (53).…”

Section: Metabolism Of P-450 Substratesmentioning

confidence: 99%

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Biotransformation Enzymes in the Rodent Nasal Mucosa: The Value of a Histochemical Approach

Bogdanffy¹

1990

Environmental Health Perspectives

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An increasing number of chemicals have been identified as being toxic to the nasal mucosa of rats. While many chemicals exert their effects only after inhalation exposure, others are toxic following systemic administration, suggesting that factors other than direct deposition on the nasal mucosa may be important in mechanisms of nasal toxicity. The mucosal lining of the nasal cavity consists of a heterogeneous population of ciliated and nonciliated cells, secretory cells, sensory cells, and glandular and other cell types. For chemicals that are metabolized in the nasal mucosa, the balance between metabolic activation and detoxication within a cell type may be a key factor in determining whether that cell type will be a target for toxicity. Recent research in the area of xenobiotic metabolism in nasal mucosa has demonstrated the presence of many enzymes previously described in other tissues. In particular, carboxylesterase, aldehyde dehydrogenase, cytochromes P-450, epoxide hydrolase, and glutathione S-transferases have been localized by histochemical techniques. The distribution of these enzymes appears to be cell-type-specific and the presence of the enzyme may predispose particular cell types to enhanced susceptibility or resistance to chemical-induced injury. This paper reviews the distribution of these enzymes within the nasal mucosa in the context oftheir contribution to xenobiotic metabolism. The localization of the enzymes by histochemical techniques has provided important information on the potential mechanism of action of esters, aldehydes, and cytochrome P-450 substrates known to injure the nasal mucosa.

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Section: Metabolism Of P-450 Substratesmentioning

confidence: 84%

Section: Metabolism Of P-450 Substratesmentioning

confidence: 99%

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Biotransformation Enzymes in the Rodent Nasal Mucosa: The Value of a Histochemical Approach

Bogdanffy¹

1990

Environmental Health Perspectives

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“…On induction with Aroclor 1254, benzo(a)pyrene hydroxylase, but not cytochromes P-450, BNF-B, or 3-methylcholanthrene (MC-B), were induced throughout the bronchial and bronchiolar epithelia, suggesting that other immunochemically unrelated cytochrome P-450 isozymes were induced (42).…”

Section: Pulmonary Metabolism Of Chemicals In Relation To Their Toxicitymentioning

confidence: 99%

“…By using autoradiographic and immunohistochemical methods, it was shown that much of the total lung content of cytochrome P-450, the mixed-function oxidase responsible for the activation of many chemicals to reactive metabolites, was localized in the nonciliated bronchiolar epithelial (Clara) cells (38,39 showed that the bronchus, bronchiole, and alveolar walls contained antigens related to NADPH-cytochrome P-450 reductase; cytochromes P-450, phenobarbitone (PB-B), and pregnanalone-16a-carbonitrile (PCN-E); epoxide hydrolase; and glutathione S-transferases B, C, and E; but only very low levels of cytochrome P-450, f3-naphthoflavone (BNF-B) (42). On induction with Aroclor 1254, benzo(a)pyrene hydroxylase, but not cytochromes P-450, BNF-B, or 3-methylcholanthrene (MC-B), were induced throughout the bronchial and bronchiolar epithelia, suggesting that other immunochemically unrelated cytochrome P-450 isozymes were induced (42).…”

Section: Pulmonary Metabolism Of Chemicals In Relation To Their Toxicitymentioning

confidence: 99%

Pulmonary Metabolism of Foreign Compounds: Its Role in Metabolic Activation

Cohen¹

1990

Environmental Health Perspectives

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The lung has the potential of metabolizing many foreign chemicals to a vast array ofmetabolites with different pharmacological and toxicological properties. Because many chemicals require metabolic activation in order to exert their toxicity, the cellular distribution of the drug-metabolizing enzymes in a heterogeneous tissue, such as the lung, and the balance of metabolic activation and deactivation pathways in any particular cell are key factors in determining the cellular specificity ofmany pulmonary toxins. Enviroxnmental factors such as air pollution, cigarette smoking, and diet markedly affect the pulmonary metabolism of some chemicals and, thereby, possibly affect their toxicity.

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Pulmonary Epithelium: Cell Types and Functions

Chang

Shih

2008

The Pulmonary Epithelium in Health and Disease

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Sites for xenobiotic activation and detoxication within the respiratory tract: Implications for chemically induced toxicity

Cited by 59 publications

References 39 publications

Biotransformation Enzymes in the Rodent Nasal Mucosa: The Value of a Histochemical Approach

Biotransformation Enzymes in the Rodent Nasal Mucosa: The Value of a Histochemical Approach

Pulmonary Metabolism of Foreign Compounds: Its Role in Metabolic Activation

Pulmonary Epithelium: Cell Types and Functions

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