Reference SummaryPaulsen JE, Carcinogenesis 1999 Jul;20(7):1277-82

Title

Neonatal exposure to the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine via breast milk or directly induces intestinal tumors in multiple intestinal neoplasia mice.

Authors

Paulsen JE; Steffensen IL; Andreassen A; Vikse R; Alexander J

Journal

Carcinogenesis

Volume

20

Issue

7

Year

1999

Pages

1277-82

Abstract

We examined whether the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) could increase intestinal tumorigenesis in neonatal C57BL/6J-Min/+ mice, a murine model for familial adenomatous polyposis. Min/+ mice are heterozygous for a nonsense mutation in the adenomatous polyposis coli gene and spontaneously develop multiple intestinal adenomas, primarily in the small intestine. Neonatal Min/+ mice (3-6 days old) were exposed to PhIP via breast milk from lactating dams given 8 s.c. injections of 50 mg/kg PhIP three times a week or to 8 s.c. injections of 25 or 50 mg/kg PhIP directly, over the same period. At the age of 11 weeks, the number, diameter and location of the intestinal tumors were scored. Remarkably, a 2- to 4-fold increase in the number of small intestinal tumors was seen in Min/+ mice exposed to PhIP via breast milk (P < 0.001). To our knowledge, this is the first time PhIP has been reported to induce tumors following exposure via breast milk from PhIP-exposed dams. Upon direct exposure to 50 mg/kg PhIP, a 6- to 9-fold increase in the number of small intestinal tumors was observed (P < 0.001). The diameter of the PhIP-induced small intestinal tumors was slightly increased (P < 0.001). In the colon, a 3- to 4-fold increase in the number of tumors was seen in Min/+ mice exposed to PhIP via breast milk (P = 0. 004). Direct exposure to 50 mg/kg PhIP caused a 2- to 6-fold increase in the number of colonic tumors (P = 0.014). The PhIP-induced colonic tumors were located more distally and displayed a smaller diameter than the tumors from the controls (P < 0.05). In contrast to a previous study, where PhIP showed only a moderate tumorigenic effect in adult Min/+ mice, the present study demonstrates a strong tumorigenic effect of PhIP in neonatally exposed Min/+ mice, even after exposure via breast milk from PhIP-exposed dams.

Links

J:56392 – Mouse Genome Informatics
10383901 – National Library of Medicine/PubMed

Models

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

32 - 47

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

50 - 100

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

100

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

100