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

We examined whether the food mutagen 2-amino-1-methyl-6-phenylimidazo [3,5-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 darns. Upon direct exposure to 50 mg/kg PhIP, a 6- tb 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.