Molecular regulation of genes encoding xenobiotic-metabolizing enzymes: Mechanisms involving endogenous factors

It is widely recognized that xenobiotic-metabolizing enzymes play a fundame ntal role in the basic processes of carcinogenesis and toxicity on one hand , and chemoprevention and drug efficacy on the other. Realization that diff erent factors can profoundly affect the expression of these enzymes at the genome level has resulted in an enhanced appreciation of the importance the se genes play in our modern industrialized age. There continues to be rapid proliferation of studies addressing the molecular regulation of these gene s. The discovery of common signal transduction pathways and transcription f actors that dictate tissue and developmental-specific expression, as well a s variation in expression within a given tissue, suggest that there may be significant interaction among these various regulatory systems. This report is a summary of a symposium that was part of the Structure, Function and R egulation of Cytochromes P450 and Xenobiotic Metabolizing Enzymes satellite meeting of the 2000 joint meeting of the American Society for Biochemistry and Molecular Biology, the American Society for Pharmacology and Experimen tal Therapeutics, the French Pharmacological Society, and the Pharmacologic al Society of Canada held in Boston, Massachusetts. This symposium brought together several speakers who addressed specific receptor-mediated signal t ransduction pathways involved in the regulation of xenobiotic-metabolizing enzymes, as well as other molecular mechanisms whereby endogenous factors a re involved in controlling tissue- and developmental-specific expression.