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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

Colonic lesion development in A/J Min/+ mice fed four different diets; (△) Control; (●) Hemin; (◇) Hemin+Nitrite; (■) Nitrite.A-C shows data for flat ACF, while D-F presents data for colonic tumors. A and D) Number of lesions, B and E) size of lesions, C and F) flat ACF load and tumor load, respectively. Values represent the mean, error bars show the 95% confidence interval. Horizontal bars indicate significant difference between the groups.
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pone.0122880.g001: Colonic lesion development in A/J Min/+ mice fed four different diets; (△) Control; (●) Hemin; (◇) Hemin+Nitrite; (■) Nitrite.A-C shows data for flat ACF, while D-F presents data for colonic tumors. A and D) Number of lesions, B and E) size of lesions, C and F) flat ACF load and tumor load, respectively. Values represent the mean, error bars show the 95% confidence interval. Horizontal bars indicate significant difference between the groups.

Mentions: In the colon, two types of lesions were observed; flat ACF and tumors (Fig 1 and S1 Fig). The number of flat ACF observed in the colon of mice fed diets Hemin or Hemin+Nitrite was significantly lower than in mice fed Nitrite or Control. The size of flat ACF did not differ between mice fed the four different diets. Nevertheless, a tendency for slightly smaller flat ACFs was seen in both Hemin and Hemin+Nitrite fed animals, although not significant. The total area of flat ACF per mouse (flat ACF load) was significantly lower in mice fed Hemin or Hemin+Nitrite than in mice fed Nitrite or Control. When compared with flat ACF, the mice had few colonic tumors. Interestingly, the patterns of tumor number (p = 0.090), tumor size and tumor load (p = 0.075) observed in animals fed the four experimental diets were similar to those observed for flat ACF. However, the differences in tumor scores did not achieve statistical significance.


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)

Colonic lesion development in A/J Min/+ mice fed four different diets; (△) Control; (●) Hemin; (◇) Hemin+Nitrite; (■) Nitrite.A-C shows data for flat ACF, while D-F presents data for colonic tumors. A and D) Number of lesions, B and E) size of lesions, C and F) flat ACF load and tumor load, respectively. Values represent the mean, error bars show the 95% confidence interval. Horizontal bars indicate significant difference between the groups.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0122880.g001: Colonic lesion development in A/J Min/+ mice fed four different diets; (△) Control; (●) Hemin; (◇) Hemin+Nitrite; (■) Nitrite.A-C shows data for flat ACF, while D-F presents data for colonic tumors. A and D) Number of lesions, B and E) size of lesions, C and F) flat ACF load and tumor load, respectively. Values represent the mean, error bars show the 95% confidence interval. Horizontal bars indicate significant difference between the groups.
Mentions: In the colon, two types of lesions were observed; flat ACF and tumors (Fig 1 and S1 Fig). The number of flat ACF observed in the colon of mice fed diets Hemin or Hemin+Nitrite was significantly lower than in mice fed Nitrite or Control. The size of flat ACF did not differ between mice fed the four different diets. Nevertheless, a tendency for slightly smaller flat ACFs was seen in both Hemin and Hemin+Nitrite fed animals, although not significant. The total area of flat ACF per mouse (flat ACF load) was significantly lower in mice fed Hemin or Hemin+Nitrite than in mice fed Nitrite or Control. When compared with flat ACF, the mice had few colonic tumors. Interestingly, the patterns of tumor number (p = 0.090), tumor size and tumor load (p = 0.075) observed in animals fed the four experimental diets were similar to those observed for flat ACF. However, the differences in tumor scores did not achieve statistical significance.

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