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 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.
Sørensen
I K
IK
National Food Agency, Institute of Toxicology, Søborg, Denmark.
Kristiansen
E
E
Mortensen
A
A
van Kranen
H
H
van Kreijl
C
C
Fodde
R
R
Thorgeirsson
S S
SS
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*
D007093:Imidazoles; D009153:Mutagens; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine