title: Short-term carcinogenicity testing of a potent murine intestinal mutagen, 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), in Apc1638N transgenic mice.
abstract: Transgenic Apc1638N mice, heterozygous for a targeted frameshift mutation at codon 1638 of the endogenous adenomatous polyposis coli (APC) gene, are predisposed to develop multiple adenomas and adenocarcinomas along the intestinal tract and to a number of extra-intestinal lesions including, among others, mammary tumors. We have studied these mice in a short-term carcinogenicity test with 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), a potent murine small intestinal mutagen and lymphomagen. Upon dietary administration of 0.03% PhIP in a short-term (6 months) study, a significantly increased number of small intestinal tumors as well as an increased number of aberrant crypt foci (ACF) were observed in male Apc+/Apc1638N mice compared with untreated transgenic mice. No differences in intestinal and mammary tumor multiplicity were observed between treated and control Apc+/Apc1638N females.
authors.affiliation: National Food Agency, Institute of Toxicology, Søborg, Denmark.
authors.forename: I K
authors.initials: IK
authors.lastname: Sørensen
authors.forename: E
authors.initials: E
authors.lastname: Kristiansen
authors.forename: A
authors.initials: A
authors.lastname: Mortensen
authors.forename: H
authors.initials: H
authors.lastname: van Kranen
authors.forename: C
authors.initials: C
authors.lastname: van Kreijl
authors.forename: R
authors.initials: R
authors.lastname: Fodde
authors.forename: S S
authors.initials: SS
authors.lastname: Thorgeirsson
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D005260:Female; D016368:Frameshift Mutation; D017491:Genes, APC; D007093:Imidazoles / Q000633:toxicity*; D007414:Intestinal Neoplasms / Q000139:chemically induced; D007422:Intestines / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009153:Mutagens / Q000633:toxicity*
chemical_list: D007093:Imidazoles; D009153:Mutagens; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine