Olfactory epithelium tissues

Smolowitz, R.M., M.E. Schultz, and J.J. Stegeman. 1992. Cytochrome P450A1 induction in tissues, including olfactory epithelium, of topminnows (Poeciliopsis spp.) by waterborne benzo[a]pyrene. Carcinogenesis 13 2395-2402. 

No neoplastic effect was observed in rats exposed to 0, 15, 45, or 135ppm for 6 hours/ day, 5 days/week for 2 years. Dose-related changes, which include atrophy of the neurogenic epithelial cells and hyperplasia of the reserve cells, mainly affected the anterior part of the olfactory epithelium. In the high-dose group there was opacity of the cornea. After a 6-month postexposure period reconstructive effects were observed in both tissues. 

This tissue is known to contain a high level of cytochromes P-450 activity. Clearly, it is similar to the lung in exposure. An example is the industrial chemical trifluoromethylpyridine, which specifically damages the olfactory epithelium in animals exposed to it in the inspired air. The compound is metabolized by N-oxidation, and the N-oxide product (or a nitroxide radical) is believed to be responsible for the toxicity (chap. 4, Fig. 20). The activity for this metabolic pathway is particularly high in the olfactory epithelium. 

Male and female Fischer 344 rats and B6C3Fj mice were exposed to 3, 15 or 75 ppm [23, 115 or 577 mg/m J ethylene dibromide for 6 h per day on five days per week for 13 weeks. Rats and mice examined after 13 weeks of exposure showed severe necrosis and atrophy of the olfactory epithelium in the nasal cavity after inhalation of 75 ppm ethylene dibromide. Lower concentrations induced squamous-cell metaplasia, hyperplasia and cytomegaly of the epithelium of the respiratory nasal turbinates. Metaplasia, hyperplasia and epithelial cytomegaly were also seen in other respiratory tissues (larynx, trachea, bronchi, bronchioles) at this dose (Reznik et al., 1980). 

Mammalian pheromones released into their environment can readily reach their target tissue, either the main olfactory epithelium (MOE) or the VNO. Both target tissues are lined with an olfactory neuroepithelium that contains membrane-bound receptor proteins, which comprise the largest known family of G-protein-coupled [262] receptors in mammals. The number of mammalian olfactory receptors [263-265] found has been astonishing, but not unreasonable. The MOE and VNO have some common features, but also significant difierences in neuron types, primary structures of receptor proteins and signal transduction [266]. 

Following an oral gavage for 90 days, the no-effect-dose is 8 mg kg day, with severe forestomach tissue lesions characterized by inflammation, necrosis, acantholysis, hyperkeratosis, and epithelial hyperplasia. Mice exposed to 8 ppm chloropicrin vapor for 6 h day for 5 days developed moderate to severe degeneration of the respiratory and olfactory epithelium as well as fibrosing peribronchitis and peribronchiolitis of the lung. 

When critical levels of exposure to the ensuing acetaldehyde and acetic acid are achieved, thresholds are exceeded and further critical steps in the mechanism ultimately leading to cancer become active. These steps are illustrated for olfactory epithelium inFigure 14. The PBPK model predicts that in rat nasal olfactory tissue, exposure to 50-ppru vinyl acetate causes a 0.08 unit reduction in pHj and abasal cell acetaldehyde concentration of 1.7 /xg/ruL. Fifty-ppm vinyl acetate is a NOAEL,... 

Fig. 4 Expression profile of human OR genes across tissues and variation in three human samples. The log transformed detection P values for OR genes in all tissues were standardized to have a mean of 0 and a standard deviation of 1 and are color coded (red and blue shades indicate values above and below the mean, respectively). The dendrograms on top of each panel illustrate the clustering of tissue samples based on the profile of OR gene expression, (a) All 578 predicted OR genes are included in a comparison between olfactory epithelium (OE) and non olfactory tissues, (b) Shown are the data for only the 147 OR genes with significantly elevated expression in non olfactory tissues, (c) The number of predicted human OR genes whose expression was detected (at P < 0.05) in one or more of the three olfactory epithelium (OE) samples. As can be seen, there is a substantial difference in the expressed OR gene repertoire of each of the three OE samples...

Under normal conditions, most nonvolatile chemicals cannot reach the human olfactory epithelium and so are unable to stimulate olfaction. However, such molecules, when presented as aerosols, can reach the sensory tissue and can then stimulate a response. Odorants are typically small, hydrophobic, organic molecules with a mass range of 34-300 Da. Most odorants contain a single polar group. The majority of odorants contain oxygen. 

The olfactory receptor cells are located in the olfactory epithelium. This is a greenish-yellowish patch of tissue, several square centimetres in area, which is found on the roof of the nasal cavity, as shown in Figure 13.8. The epithelium is about 100-200 pm thick and is bathed in an aqueous liquid known as the olfactory mucus. The mucus is about 35 pm thick and flows backwards across the epithelium at about l-6cm/min. The receptor cells run through the cribriform plate at the base of the skull. At one end (in the epithelium) the cells contain hairs, or cilia, which are 20-200 pm long and which is where the receptor proteins are located. 

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