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Scientists from Canadian institutions have a rich history of making interesting and important contributions to the journal (DMD) over the past 51 years. A goal of this minireview is to highlight these contributions and pay tribute to many of the scientists at Canadian institutions that have aided in the evolution of the discipline through their DMD publications. We conducted a geographical and research sectoral analysis of the temporal trends of DMD publications originating from Canadian sources.

Fifty Years of Aryl Hydrocarbon Receptor Research as Reflected in the Pages of .

The induction of multiple drug-metabolizing enzymes by halogenated and polycyclic aromatic hydrocarbon toxicants is mediated by the aryl hydrocarbon receptor (AHR). This fascinating receptor also has natural dietary and endogenous ligands, and much is now appreciated about the AHR's developmental and physiologic roles, as well as its importance in cancer and other diseases. The past several years has witnessed increasing emphasis on understanding the multifaceted roles of the AHR in the immune system.

Mechanisms of NADPH - cytochrome P450 oxidoreductase induction by dexamethasone in the H4IIE rat hepatoma cell line.

Expression of NADPH - cytochrome P450 oxidoreductase (POR), electron donor for microsomal P450s, is induced in rat liver by dexamethasone (DEX), an activator of the glucocorticoid receptor (GR) and the pregnane X receptor (PXR). DEX induction of POR in rat liver is primarily PXR-mediated, although GR may contribute to mRNA effects. We examined the role of GR and PXR in the DEX induction of POR mRNA and protein in the H4IIE rat hepatoma cell line.

Suppression of Hepatic Expression and Activity by 3-Methylcholanthrene in Humanized PXR-CAR-CYP3A4/3A7 Mice.

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants that activate the aryl hydrocarbon receptor, thereby triggering a range of biologic responses, exemplified by the induction of PAHs can also regulate the expression of members of the subfamily, with reports of mainly suppressive effects on mouse hepatic expression, but paradoxically both inductive and suppressive effects on human hepatic expression. Understanding the regulation of expression by PAHs is important because of the widespread exposure of humans to these chemicals and the central role of the CYP3A4 enzyme in the metabolism of clinically important drugs and endogenous substances. The present study used 3-methylcholanthrene (MC) as a model PAH to characterize the in vivo regulation of expression and activity in humanized pregnane X receptor-constitutive androstane receptor-CYP3A4/3A7 mice.

Downregulation of cytochrome P450 2C8 by 3-methylcholanthrene in human hepatocellular carcinoma cell lines.

The marked induction of cytochromes P450 such as CYP1A1 caused by polycyclic aromatic hydrocarbons (PAHs) like 3-methylcholanthrene (MC) is often accompanied by suppression of other hepatic P450s. The molecular mechanisms, functional consequences, and human relevance of P450 downregulation by PAHs are poorly understood. MC suppresses mRNA levels for CYP2C8, an important human P450, in cultured human hepatocytes.