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

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 ot...

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Bibliographic Details
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
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Summary: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.
ISSN:0143-3334
1460-2180
1460-2180
DOI:10.1093/carcin/18.4.777