Cytochrome P-450-Dependent Monooxygenases in Olfactory Epithelium of Dogs: Possible Role in Tumorigenicity

Dahl, Alan R.; Hadley, William M.; Hahn, Fletcher F.; Benson, Janet M.; McClellan, R.O.

doi:10.1126/science.7063870

Cited by 139 publications

(50 citation statements)

References 9 publications

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“…Sus and ensheathing glia derived apoE could be critically involved in recycling of membrane components liberated from the senescing ORN population and recycling it to support basal cell division and differentiation and axonal elongation of the newly differentiated ORN. We propose that Sus-derived apoE facilitates the various functions attributed to Sus and ensheathing glia (Barnett, 2004;Dahl et al, 1982;Getchell et al, 1984;Ramon-Cueto and Avila, 1998).…”

Section: Discussionmentioning

confidence: 99%

The distribution of apolipoprotein E in mouse olfactory epithelium

Nathan¹,

Nannapaneni²,

Gairhe³

et al. 2007

Brain Research

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Previous studies from our laboratory suggest that apolipoprotein (apoE), a lipid transporting protein, facilitates olfactory nerve regeneration. We have shown that apoE is enriched in the olfactory nerve and around the glomeruli of the olfactory bulb (OB). The studies reported herein were undertaken to identify possible sources of apoE in the olfactory epithelium (OE). Immunoblotting results revealed apoE expression in the OE of wild-type (WT) mice, but not in apoE deficient/knockout (KO) mice. Immunohistochemical studies revealed that the perikarya and processes of sustentacular (Sus) cells expressed apoE-like immunoreactivity. Minimal neuronal apoE immunostaining was seen, although apoE was observed in the interstial spaces between olfactory receptor neurons (ORN). Substantial apoE-like immunoreactivity was localized to the endfeet and terminal process of Sus cells surrounding the basal cells. Double labeling immunocytochemical studies confirmed that the cell bodies and endfeet of Sus cells expressed high levels of apoE. The endothelial cells of blood vessels were intensely stained for apoE in the lamina propria. Cells forming Bowman's gland also immunostained for apoE. The apoE staining in the nerve fascicles was less intense, but was uniformly distributed throughout the core of the nerve bundles. Heavily stained cells, probably ensheathing glia, surrounded the nerve fascicles. These results revealed that apoE is expressed in the adult OE and lamina propria at strategic locations where it could facilitate the differentiation, maturation and axonal growth of the ORN, perhaps by recycling lipids from degenerating ORN for use by growing axons.

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Section: Discussionmentioning

confidence: 99%

The distribution of apolipoprotein E in mouse olfactory epithelium

Nathan¹,

Nannapaneni²,

Gairhe³

et al. 2007

Brain Research

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“…Luminal nonciliated cells in rodents, however, have abundant apical accumulations of agranula endoplasmic reticulum (aER), a feature not evident in similar cells in macaque monkeys. Relatively high amounts of cytochrome P-450-dependent monooxygenase (usually associated with aER) have been reported in the rat, rabbit, and dog nasal mucosa, covering the anterior nasal cavity (23,24). The anterior aspect of the dorsal concha of the dog nasal cavity, a region covered by TE, has recently been shown to have higher metabolizing activity for certain xenobiotic substrates than other regions of canine nasal mucosa (25).…”

Section: Nasal Epithelial Populationsmentioning

confidence: 99%

Comparative Pathology of the Nasal Mucosa in Laboratory Animals Exposed to Inhaled Irritants

Harkema¹

1990

Environmental Health Perspectives

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The nasal cavity is susceptible to chemically induced iinjury as a result of exposure to inhaled irritants. Some responses of the nasal mucosa to inhaled toxicants are species specific. These species-related differences in response may be due to variations in structural, physiologic, and biochemical factors, such as gross nasal cavity structure, distribution of luminal epithelial cell populations along the nasal airway, intranasal airflow patterns, nasal mucociliary apparatus, and nasal xenobiotic metabolism among animal species. This paper reviews the comparative anatomy and irritant-induced pathology of the nasal cavity in laboratory animals. The toxicologist, pathologist, and environmental risk assessor must have a good working knowledge of the similarities and differences in normal nasal structure and response to injury among species before they can select animal models for nasal toxicity studies, recognize toxicantinduced lesions in the nasal airway, and extrapolate experimental results to estimate the possible effects of an inhaled toxicant on the human nasal airway.

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“…The latter studies were of particular importance since they suggested that agents reaching the nasal mucosa through the systemic circulation may be metabolically activated within target cells. Prior to 1982 when the group at Lovelace Inhalation Toxicology Research Institute first demonstrated the susceptibility of the rat and dog nasal mucosa to N-demethylate, a variety of cytochrome P-450 substrates, no other work had highlighted the potential importance of this tissue as a site for extrahepatic xenobiotic metabolism (8,9).…”

Section: Introductionmentioning

confidence: 99%

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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Cytochrome P-450-Dependent Monooxygenases in Olfactory Epithelium of Dogs: Possible Role in Tumorigenicity

Cited by 139 publications

References 9 publications

The distribution of apolipoprotein E in mouse olfactory epithelium

The distribution of apolipoprotein E in mouse olfactory epithelium

Comparative Pathology of the Nasal Mucosa in Laboratory Animals Exposed to Inhaled Irritants

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

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