title: Comparative biotransformation studies of MeIQx and PhIP in animal models and humans.
abstract: MeIQx and PhIP are putative carcinogenic heterocyclic amines formed during the cooking of meat and fish. Using accelerator mass spectrometry, we have investigated the metabolism and macromolecule binding of 14C-labelled MeIQx and PhIP in human cancer patients compared to the rat. Following oral administration of MeIQx and PhIP, more DNA adducts were formed in human colon tissue compared with rats. Differences were also observed between rats and humans in the metabolite profile and urine excretion for these compounds. These results suggest humans metabolise heterocyclic amines differently to laboratory rodents and question their use as models of human risk.
authors.affiliation: JBUEC, Department of Biology, University of York, UK. rcg2@york.ac.uk
authors.forename: R C
authors.initials: RC
authors.lastname: Garner
authors.forename: T J
authors.initials: TJ
authors.lastname: Lightfoot
authors.forename: B C
authors.initials: BC
authors.lastname: Cupid
authors.forename: D
authors.initials: D
authors.lastname: Russell
authors.forename: J M
authors.initials: JM
authors.lastname: Coxhead
authors.forename: W
authors.initials: W
authors.lastname: Kutschera
authors.forename: A
authors.initials: A
authors.lastname: Priller
authors.forename: W
authors.initials: W
authors.lastname: Rom
authors.forename: P
authors.initials: P
authors.lastname: Steier
authors.forename: D J
authors.initials: DJ
authors.lastname: Alexander
authors.forename: S H
authors.initials: SH
authors.lastname: Leveson
authors.forename: K H
authors.initials: KH
authors.lastname: Dingley
authors.forename: R J
authors.initials: RJ
authors.lastname: Mauthe
authors.forename: K W
authors.initials: KW
authors.lastname: Turteltaub
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes; D002273:Carcinogens / Q000008:administration & dosage / Q000378:metabolism*; D003106:Colon / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000378:metabolism*; D011810:Quinoxalines / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D013045:Species Specificity
chemical_list: D002250:Carbon Radioisotopes; D002273:Carcinogens; D018736:DNA Adducts; D007093:Imidazoles; D011810:Quinoxalines; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine