CYP2A1O and CYP2A11, which are abundant in olfactory microsomes from rabbits, are active in the metabolic activation of a number of nasal toxicants, such as hexamethylphosphoramide and N-nitrosodiethylamine. Previous immunohistochemical studies indicated that CYP2A-related cytochromes P450 may also be present in rodent and human olfactory tissue. In the present study, the expression of cytochromes P450 highly homologous to rabbit CYP2A10/11 in rat, mouse, and human nasal mucosa was studied. In Sprague-Dawley rats, CYP2A3 mRNA was detected in olfactory mucosa at levels much higher than those found in total RNA from lung. Similar observations were made for the level of microsomal CYP2A3 protein with the use of antibodies to rabbit CYP2A10/11. However, mRNAs for two other rat cytochrome P450 genes in the CYP2A subfamily, CYP2A1 and CYP2A2, were not detected in nasal tissue by RNA-polymerase chain reaction analysis. In C57BL/6 mice, both CYP2A4 and CYP2A5 mRNAs were detected in the olfactory mucosa by RNA- polymerase chain reaction, but the CYP2A5 transcript was present at a level much higher than that of CYP2A4. The expression of another mouse gene in the CYP2A subfamily, CYP2A12, was not detected in nasal tissue. CYP2A5 protein was also detected in mouse olfactory microsomes at higher levels than in liver, lung, or kidney microsomes. However, no significant sex differences in the levels of CYP2A4/5 mRNA or microsomal coumarin 7-hydroxylase activity were found with the nasal tissue. In addition, consistent with previous immunohistochemical studies, the expression of CYP2A6 in human nasal mucosa was detected by RNA-polymerase chain reaction as well as RNA blot analysis. The identification of CYP2A6 in human nasal tissues may have important implications for risk assessment of potential nasal toxicants, and the abundant expression of the CYP2A genes in rat and mouse olfactory tissue suggests a molecular basis for the known tissue-specific toxicity of numerous inhaled compounds in rodents.
|Original language||English (US)|
|Number of pages||7|
|Journal||Drug Metabolism and Disposition|
|State||Published - Aug 1996|
ASJC Scopus subject areas
- Pharmaceutical Science