INDUCTION OF NASAL CARBOXYLESTERASE IN F344 RATS FOLLOWING INHALATIONEXPOSURE TO PYRIDINE

Carboxylesterases (CEs) in the nasal mucosa metabolize some inhaled es ters, including industrially important acrylates and acetates, to toxi c acid metabolites that produce site-specific lesions in the nasal epi thelium. The metabolic capacity of CEs in the normal nasal mucosa is t heoretically sufficient to protect the lower respiratory tract from to xicant-induced injury at concentrations of acrylates and acetates like ly to be inhaled in industrial environments. Thus, alterations in the metabolism and toxicity of these substrates would be predicted with ch anges in the amount or activity of CE in the nasal mucosa. Although ma ny other nasal enzymes have been reported to be relatively refractory to induction, the amount of CE in the nasal mucosa can be increased by inhalant exposure. In the liver, expression of CEs may be elevated in response to exposure to P450 inducers. To examine this phenomenon in the nose with the widely used industrial solvent pyridine, we examined the effect of pyridine inhalation at the threshold limit value concen tration of 5 ppm, or at 444 ppm, 6 hr/day for 4 days on the localizati on and amount of immunoreactive CE in olfactory mucosas of F344/N rats . CE immunoreactivity was increased in Bowman's glands following expos ure to 5 or 444 ppm pyridine, and in sustentacular cells most notably following the 5 ppm exposure. Quantitative densitometry showed a stati stically significant, dose-related increase in the density of immunore active CE in Bowman's glands of pyridine-exposed rats. These results i ndicate pyridine, and possibly other solvents, can induce nasal CE, an enzyme not directly involved in the metabolism of those solvents, fol lowing low-dose, short-term exposure. Previous results show loss of CE with some nasal lesions. The labile nature of this enzyme emphasizes the need to consider exposure history when predicting risk due to toxi cant exposure, especially for toxicants that are metabolized.