Reference SummaryMollersen L, Mutat Res 2004 Jan 10;557(1):29-40


Adenomatous polyposis coli truncation mutations in 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced intestinal tumours of multiple intestinal neoplasia mice.


Mollersen L; Vikse R; Andreassen A; Steffensen IL; Mikalsen A; Paulsen JE; Alexander J


Mutat Res










The heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induces intestinal tumours in C57BL/6J-multiple intestinal neoplasia (Min)/+ mice. The main mechanism for PhIP-induced tumour induction in Min/+ mice is loss of the wild-type adenomatous polyposis coli (Apc) allele, i.e. loss of heterozygosity (LOH). In this study, single injections of either 10, 17.5 or 25mg/kg PhIP on days 3-6 after birth all increased the mean number of small intestinal tumours two to three-fold, from 37.7 in controls to 124.8 in the PhIP-treated Min/+ mice. In total, we analysed 292 small intestinal tumours and 253 of these had LOH. The frequency of LOH in the Apc gene was 88, 93, 83 and 84% in tumours of 0, 10, 17.5 and 25mg/kg PhIP-treated mice, respectively. Therefore, these lower doses of PhIP did not reduce the frequency of LOH, as found in our previous study with a single injection of 50mg/kg PhIP (Mutat. Res. 1-2 (2002) 157). In the second part of this study, we wanted to characterise Apc truncation mutations from tumour samples apparently retaining the Apc wild-type allele from this and two previous experiments with PhIP-exposed Min/+ mice. In the first half of exon 15 in Apc, we verified 25 mutations from 804 tumour samples of PhIP-treated mice. Of these were 60% G-->T transversions, and 16% G deletions, indicating that these are the predominant types of PhIP-induced truncation mutations in the Apc gene in Min/+ mice. Most of the mutations were located between codon 989 and 1156 corresponding to the first part of the beta-catenin binding region. We also identified two Apc truncation mutations from 606 spontaneously formed intestinal tumours from untreated Min/+ mice, one C-->T transition and one T insertion, which were different from those induced by PhIP.


J:87470 – MGI References
14706516 – National Library of Medicine/PubMed

Strain Notes

Strain Note
C57BL/6J-ApcMin/+ Mice were bred at the Norwegian Institute of public Health, Oslo, Norway from mice originally purchased from The Jackson Laboratory.


Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
C57BL/6J-ApcMin/+ Intestine - Large Intestine - Colon tumor Intestine - Large Intestine - Colon


C57BL/6J-ApcMin/+ Intestine - Large Intestine - Colon tumor
  • 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)
Intestine - Large Intestine - Colon

80 - 92

C57BL/6J-ApcMin/+ Intestine - Small Intestine tumor Intestine - Small Intestine

observed - 100

C57BL/6J-ApcMin/+ Intestine - Small Intestine tumor
  • 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)
Intestine - Small Intestine

observed - 100