title: Metabolic Activation of Heterocyclic Amines and Expression of Xenobiotic-Metabolizing Enzymes in the Gastrointestinal Tract of Rats.
abstract: Heterocyclic amines get entry into human body mainly through ingestion of pan-fried meats cooked at high temperatures. Exposure of the gastrointestinal tract (GIT) to ingested xenobiotics prior to delivery to the liver may lead to metabolic activation, which may explain the high incidence of GIT carcinogenesis. Therefore, this study investigated the mutagenic activation of 2 heterocyclic amines, 2-aminoanthracene (2-AA) and 3-amino-1-methyl-5H-prydo[4,3-b]indole (Trp-P-2), in the GIT of rats. In addition, the constitutive mRNA expression profiles of xenobiotic-metabolizing enzymes (XMEs) in the GIT of rats were examined. Metabolic activation of 2-AA was detected in all GIT tissues except the duodenum and rectum, and it was detected at high levels in the ileum and cecum. Furthermore, we revealed high metabolic activation of 2-AA and Trp-P-2 in the jejunum. The mRNA expression of phase I and II enzymes in rat GIT corresponded with their mutagenic activation ability. In conclusion, our results suggest that different expression levels of XME among GIT tissues may contribute to the tissue-specific differences in metabolic activation of xenobiotics such as heterocyclic amines in rats.
  
  
  CONCLUSIONS
  This study declares mutagenic activation of 2 heterocyclic amines namely 2-aminoanthracene (2-AA) and 3-amino-1-methyl-5H-prydo[4,3-b]indole (Trp-P-2), in the gastrointestinal tract (GIT) of rats. In addition, results obtained in this study suggest that GIT tissue-specific expression of xenobiotic metabolizing enzymes may contribute to the tissue-specific mutagenesis/carcinogenesis.
authors.affiliation: Laboratory of Toxicology, Dept. of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido Univ, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan.|Food Control Dept, Faculty of Veterinary Medicine, Zagazig Univ, Zagazig, 44510, Egypt.
authors.forename: Wageh S
authors.initials: WS
authors.lastname: Darwish
authors.affiliation: Laboratory of Toxicology, Dept. of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido Univ, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan.
authors.forename: Shouta M M
authors.initials: SM
authors.lastname: Nakayama
authors.affiliation: Laboratory of Toxicology, Dept. of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido Univ, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan.
authors.forename: Yuumi
authors.initials: Y
authors.lastname: Itotani
authors.affiliation: Laboratory of Toxicology, Dept. of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido Univ, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan.
authors.forename: Marumi
authors.initials: M
authors.lastname: Ohno
authors.affiliation: Laboratory of Toxicology, Dept. of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido Univ, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ikenaka
authors.affiliation: Laboratory of Toxicology, Dept. of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido Univ, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ishizuka
mesh_terms: D065767:Activation, Metabolic; D000588:Amines / Q000633:toxicity*; D000818:Animals; D000873:Anthracenes / Q000633:toxicity; D002243:Carbolines / Q000633:toxicity; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000201:enzymology; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016296:Mutagenesis; D009153:Mutagens / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism; D015262:Xenobiotics / Q000633:toxicity
chemical_list: D000588:Amines; D000873:Anthracenes; D002243:Carbolines; D006571:Heterocyclic Compounds; D009153:Mutagens; D012333:RNA, Messenger; D015262:Xenobiotics; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; C006593:2-anthramine; D014453:Glucuronosyltransferase; C107611:UDP-glucuronosyltransferase, UGT1A7; D015238:Sulfotransferases; C513315:Sult1c2 protein, rat
keywords: gastrointestinal tract; heterocyclic amines; xenobiotic-metabolizing enzymes