title: Biotransformation of xenobiotics in the human colon and rectum and its association with colorectal cancer.
abstract: In humans, the liver is generally considered to be the major organ contributing to drug metabolism, but studies during the last years have suggested an important role of the extra-hepatic drug metabolism. The gastrointestinal tract (GI-tract) is the major path of entry for a wide variety of compounds including food, and orally administered drugs, but also compounds - with neither nutrient nor other functional value - such as carcinogens. These compounds are metabolized by a large number of enzymes, including the cytochrome P450 (CYP), the glutathione S-transferase (GST) family, the uridine 5'-diphospho- glucuronosyltransferase (UDP-glucuronosyltransferase - UGT) superfamily, alcohol-metabolizing enzymes, sulfotransferases, etc. These enzymes can either inactivate carcinogens or, in some cases, generate reactive species with higher reactivity compared to the original compound. Most data in this field of research originate from animal or in vitro studies, wherein human studies are limited. Here, we review the human studies, in particular the studies on the phenotypic expression of these enzymes in the colon and rectum to get an impression of the actual enzyme levels in this primary organ of exposure. The aim of this review is to give a summary of currently available data on the relation between the CYP, the GST and the UGT biotransformation system and colorectal cancer obtained from clinical and epidemiological studies in humans.
authors: Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT) , Heidelberg , Germany .
authors: Jolantha
authors: J
authors: Beyerle
authors: Eva
authors: E
authors: Frei
authors: Marie
authors: M
authors: Stiborova
authors: Nina
authors: N
authors: Habermann
authors: Cornelia M
authors: CM
authors: Ulrich
mesh_terms: D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D001711:Biotransformation; D003106:Colon / Q000201:enzymology / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D012007:Rectum / Q000201:enzymology / Q000378:metabolism*; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism; D015262:Xenobiotics / Q000493:pharmacokinetics*
chemical_list: D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D001191:Arylamine N-Acetyltransferase; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D015238:Sulfotransferases
keywords: Biotransformation; UDP-glucuronosyltransferase; colorectal cancer; cytochrome P450; glutathione S-transferase