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We performed a detailed analysis of mouse cytochrome P450 2A5 (CYP2A5) expression by in situ hybridization (ISH) and immunohistochemistry (IHC) in the respiratory tissues of mice. The CYP2A5 mRNA and the corresponding protein co-localized at most sites and were predominantly detected in the olfactory region, with an expression in sustentacular cells, Bowman's gland, and duct cells. In the respiratory and transitional epithelium there was no or only weak expression. The nasolacrimal duct and the excretory ducts of nasal and salivary glands displayed expression, whereas no expression occurred in the acini. There was decreasing expression along the epithelial linings of the trachea and lower respiratory tract, whereas no expression occurred in the alveoli. The hepatic CYP2A5 inducers pyrazole and phenobarbital neither changed the CYP2A5 expression pattern nor damaged the olfactory mucosa. In contrast, the olfactory toxicants dichlobenil and methimazole induced characteristic changes. The damaged Bowman's glands displayed no expression, whereas the damaged epithelium expressed the enzyme. The CYP2A5 expression pattern is in accordance with previously reported localization of protein and DNA adducts and the toxicity of some CYP2A5 substrates. This suggests that CYP2A5 is an important determinant for the susceptibility of the nasal and respiratory epithelia to protoxicants and procarcinogens.

Numerous studies demonstrated that the use of lead (Pb)-containing ammunition is associated with mainly chronic health problems and also is a burden on the environment and wildlife. Recently, a number of reports showed evidence of undesirable acute health effects related to the use of newly developed Pb-free small-caliber ammunition. In this study, particles from leaded and Pb-free ammunition were collected in liquid collection medium, in a highly controlled chamber, while firing a pistol (9 mm) or a rifle (7.62 × 51 mm). The emitted particles were typically smaller than 4 μm, with the great majority in even smaller size ranges, as shown by gravimetrical analysis and a multistage impactor. Chemical analysis revealed significant differences in content and concentration of several metals in the particles. After administration of the liquids to alveolar and bronchial in vitro cell systems, particles were taken up by the cells; the Pb-free particles displayed higher cytotoxicity (EC50 = 2 μg/cm(2)) than particles from Pb ammunition. High correlation factors (>0.9) were found between cell death and content of copper and zinc. Particles from both Pb-containing and Pb-free ammunition were able to induce oxidative stress and the proinflammatory marker interleukin (IL)-8 in both in vitro systems. These results support previous findings that indicate an association between gunshot emissions and metal fume fever. This study demonstrates the usefulness of combining chemical data with biological in vitro responses in assessing acute toxicological effects from emissions from firing both Pb and Pb-free ammunition.