Biochemical Function of the Respiratory Tract: Metabolism of Xenobiotics

The responses of the respiratory tract to xenobiotic exposure are often related to the numerous xenobiotic metabolizing enzymes expressed there, particularly the cytochrome P450 monooxygenases, which are the focus of this article. Since the publication of the ***second edition of this volume, new information on various relevant topics continued to emerge. These topics include the expression and regulation of additional P450 isoforms, species differences in their activities toward additional respiratory toxicants, and the association of genetic polymorphisms in their genes in humans with the susceptibility of the lung to environmental toxicants, as well as the availability of genetically engineered mouse models, including "humanized" models, that can be utilized to identify the in vivo functions of these enzymes in the metabolism and toxicity of xenobiotics. The outcomes of these new studies endorse the conclusion that the selective expression and activities of the P450 enzymes in anatomical regions and specific cells impart specific susceptibilities to these cells. They also provide insights to the potential influence of systemic metabolism on risks of xenobiotic toxicity in the respiratory tract, as well as possible regional specificity of the metabolic mechanisms.