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

• Published in: Carcinogenesis (New York) 1997-04, Vol.18 (4), p.777-781
• Main Authors: SØRENSEN, I. K, KRISTIANSEN, E, MORTENSEN, A, VAN KRANEN, H, VAN KREIJL, C, FODDE, R, THORGEIRSSON, S. S
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Body Weight - drug effects; Carcinogenesis, carcinogens and anticarcinogens; Carcinogenicity Tests; Chemical agents; Female; Frameshift Mutation; Genes, APC; Imidazoles - toxicity; Intestinal Neoplasms - chemically induced; Intestines - drug effects; Intestines - pathology; Male; Medical sciences; Mice; Mice, Transgenic; Mutagens - toxicity; Tumors
• ISSN: 0143-3334; 1460-2180; 1460-2180
• DOI: 10.1093/carcin/18.4.777

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.