Molecular biology of the nasal airways: how do we assess cellular and molecular responses in the nose?

We summarize studies herein that relate to use of molecular techniques to assess mechanism of toxicant and carcinogen action on the nasal mucosa. Specifically, we present the results of an in vivo mutagenesis assay with the herbicide alachlor, which causes olfactory mucosal tumors in rats following dietary administration. A positive response was found in olfactory mucosa after 3 mo of treatment. There was no increase in mutant frequency in the adjacent nasal respiratory mucosa or in liver, which are both non-target tissues for alachlor carcinogenesis. We also summarize previous findings of gene expression studies. One on these was a GeneChip experiment aimed at elucidating the mechanism of alachlor olfactory carcinogenesis, wherein we found that oxidative stress and gelatinase genes were upregulated early in the carcinogenic process, while genes consistent with activation of Wnt signaling were activated later in the carcinogenic process. The final example presented summarizes the results of a microarray experiment designed to identify novel olfactory genes involved in the plasticity of the olfactory mucosa. Those studies identified novel olfactory mucosal genes including Sgpl1 and Pon1. In each instance, precise sampling is emphasized and proper controls are discussed, and examples of independent means of validation of genomics experiments are presented.