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Effects of hemin and nitrite on intestinal tumorigenesis in the A/J Min/+ mouse model.

Sødring M, Oostindjer M, Egelandsdal B, Paulsen JE - PLoS ONE (2015)

Bottom Line: Two pathways by which heme and CRC promotion may be linked have been suggested: fat peroxidation and N-nitrosation.However, our results also showed that the opposite occurred in the small intestine, where dietary hemin appeared to stimulate tumor growth.Furthermore, we find that nitrite, which did not have an effect in the colon, appeared to have a suppressive effect on tumor growth in the small intestine.

View Article: PubMed Central - PubMed

Affiliation: Norwegian University of Life Sciences, Department of Food Safety and Infection Biology, PO Box 8146 Dep., 0033, Oslo, Norway.

ABSTRACT
Red and processed meats are considered risk factors for colorectal cancer (CRC); however, the underlying mechanisms are still unclear. One cause for the potential link between CRC and meat is the heme iron in red meat. Two pathways by which heme and CRC promotion may be linked have been suggested: fat peroxidation and N-nitrosation. In the present work we have used the novel A/J Min/+ mouse model to test the effects of dietary hemin (a model of red meat), and hemin in combination with nitrite (a model of processed meat) on intestinal tumorigenesis. Mice were fed a low Ca2+ and vitamin D semi-synthetic diet with added hemin and/or nitrite for 8 weeks post weaning, before termination followed by excision and examination of the intestinal tract. Our results indicate that dietary hemin decreased the number of colonic lesions in the A/J Min/+ mouse. However, our results also showed that the opposite occurred in the small intestine, where dietary hemin appeared to stimulate tumor growth. Furthermore, we find that nitrite, which did not have an effect in the colon, appeared to have a suppressive effect on tumor growth in the small intestine.

No MeSH data available.


Related in: MedlinePlus

Size distribution of tumors in the small intestine of A/J Min/+ mice.A) mice fed four different diets, (△) Control; (●) Hemin; (◇) Hemin+Nitrite; (■) Nitrite, and B) mice fed diets with or without hemin, (●) Hemin+; (○) Hemin-. The smallest size class contained lesions with 1–4 crypts.
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pone.0122880.g004: Size distribution of tumors in the small intestine of A/J Min/+ mice.A) mice fed four different diets, (△) Control; (●) Hemin; (◇) Hemin+Nitrite; (■) Nitrite, and B) mice fed diets with or without hemin, (●) Hemin+; (○) Hemin-. The smallest size class contained lesions with 1–4 crypts.

Mentions: The size of small intestinal tumors was reduced in animals in the Nitrite group compared with animals in the Hemin, Hemin+Nitrite, or Control groups (Fig 3). However, the number of tumors, or tumor load did not differ significantly among animals fed the four diets. The mean sizes (Fig 3B), as well as the size distributions of the small intestinal tumors from animals (Fig 4A) fed these diets suggest that dietary hemin might stimulate tumor growth in the small intestines. This is further illustrated by the size distribution of small intestinal tumors from animals fed Hemin+ and Hemin- (Fig 4B) and their differences in calculated tumor size (P<0.001; Table 2). Also a suggestive increase (P = 0.084) in tumor load (mm2/mouse) was observed in mice fed Hemin+ as compared with mice fed Hemin- (Table 2). In contrast, the mean size of tumors in mice fed Nitrite+ significantly decreased when compared to mice fed Nitrite-, suggesting that dietary nitrite may cause a suppressive effect on tumor growth in the small intestine (Table 2).


Effects of hemin and nitrite on intestinal tumorigenesis in the A/J Min/+ mouse model.

Sødring M, Oostindjer M, Egelandsdal B, Paulsen JE - PLoS ONE (2015)

Size distribution of tumors in the small intestine of A/J Min/+ mice.A) mice fed four different diets, (△) Control; (●) Hemin; (◇) Hemin+Nitrite; (■) Nitrite, and B) mice fed diets with or without hemin, (●) Hemin+; (○) Hemin-. The smallest size class contained lesions with 1–4 crypts.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383626&req=5

pone.0122880.g004: Size distribution of tumors in the small intestine of A/J Min/+ mice.A) mice fed four different diets, (△) Control; (●) Hemin; (◇) Hemin+Nitrite; (■) Nitrite, and B) mice fed diets with or without hemin, (●) Hemin+; (○) Hemin-. The smallest size class contained lesions with 1–4 crypts.
Mentions: The size of small intestinal tumors was reduced in animals in the Nitrite group compared with animals in the Hemin, Hemin+Nitrite, or Control groups (Fig 3). However, the number of tumors, or tumor load did not differ significantly among animals fed the four diets. The mean sizes (Fig 3B), as well as the size distributions of the small intestinal tumors from animals (Fig 4A) fed these diets suggest that dietary hemin might stimulate tumor growth in the small intestines. This is further illustrated by the size distribution of small intestinal tumors from animals fed Hemin+ and Hemin- (Fig 4B) and their differences in calculated tumor size (P<0.001; Table 2). Also a suggestive increase (P = 0.084) in tumor load (mm2/mouse) was observed in mice fed Hemin+ as compared with mice fed Hemin- (Table 2). In contrast, the mean size of tumors in mice fed Nitrite+ significantly decreased when compared to mice fed Nitrite-, suggesting that dietary nitrite may cause a suppressive effect on tumor growth in the small intestine (Table 2).

Bottom Line: Two pathways by which heme and CRC promotion may be linked have been suggested: fat peroxidation and N-nitrosation.However, our results also showed that the opposite occurred in the small intestine, where dietary hemin appeared to stimulate tumor growth.Furthermore, we find that nitrite, which did not have an effect in the colon, appeared to have a suppressive effect on tumor growth in the small intestine.

View Article: PubMed Central - PubMed

Affiliation: Norwegian University of Life Sciences, Department of Food Safety and Infection Biology, PO Box 8146 Dep., 0033, Oslo, Norway.

ABSTRACT
Red and processed meats are considered risk factors for colorectal cancer (CRC); however, the underlying mechanisms are still unclear. One cause for the potential link between CRC and meat is the heme iron in red meat. Two pathways by which heme and CRC promotion may be linked have been suggested: fat peroxidation and N-nitrosation. In the present work we have used the novel A/J Min/+ mouse model to test the effects of dietary hemin (a model of red meat), and hemin in combination with nitrite (a model of processed meat) on intestinal tumorigenesis. Mice were fed a low Ca2+ and vitamin D semi-synthetic diet with added hemin and/or nitrite for 8 weeks post weaning, before termination followed by excision and examination of the intestinal tract. Our results indicate that dietary hemin decreased the number of colonic lesions in the A/J Min/+ mouse. However, our results also showed that the opposite occurred in the small intestine, where dietary hemin appeared to stimulate tumor growth. Furthermore, we find that nitrite, which did not have an effect in the colon, appeared to have a suppressive effect on tumor growth in the small intestine.

No MeSH data available.


Related in: MedlinePlus