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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 flat ACF and tumors in the colon 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. One crypt had an area of 0.002mm2.In the colon, lesions are considered tumors if they contain more than 30 crypts/lesion (approximately 0.4mm2).
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pone.0122880.g002: Size distribution of flat ACF and tumors in the colon 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. One crypt had an area of 0.002mm2.In the colon, lesions are considered tumors if they contain more than 30 crypts/lesion (approximately 0.4mm2).

Mentions: In previous studies, a continuous development from the monocryptal flat ACF to the stage of adenoma has been demonstrated; all lesions were characterized by severe dysplasia, altered control of β-catenin and rapid growth [29]. Hence, we present size distributions of pooled flat ACF and tumors to illustrate the effects of the dietary interventions (Fig 2). As expected, Hemin, or Hemin+Nitrite caused a shift towards smaller lesion sizes and fewer lesions compared with Nitrite or Control (Fig 2A). This suppressive effect was apparently due to the presence of hemin in the diet, as illustrated by the size distributions (Fig 2B) of these lesions in mice fed Hemin+ (pooled Hemin and Hemin+Nitrite) compared with mice fed Hemin- (pooled Nitrite and Control). The Two-Way ANOVA (Table 2) showed that hemin in the diet (Hemin+) caused a statistically significant reduction in the formation of flat ACF and tumors as well as in the growth of flat ACF. Typically, the load of flat ACF and tumors was reduced by approximately 60% (p<0.001 and p = 0.019, respectively). When comparing mice fed Nitrite+ (pooled Nitrite and Hemin+Nitrite) to mice fed Nitrite- (pooled Control and Hemin), no significant difference was observed (Table 2), indicating that nitrite in the diet did not have an effect in the colon of the A/J Min/+ mice.


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 flat ACF and tumors in the colon 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. One crypt had an area of 0.002mm2.In the colon, lesions are considered tumors if they contain more than 30 crypts/lesion (approximately 0.4mm2).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0122880.g002: Size distribution of flat ACF and tumors in the colon 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. One crypt had an area of 0.002mm2.In the colon, lesions are considered tumors if they contain more than 30 crypts/lesion (approximately 0.4mm2).
Mentions: In previous studies, a continuous development from the monocryptal flat ACF to the stage of adenoma has been demonstrated; all lesions were characterized by severe dysplasia, altered control of β-catenin and rapid growth [29]. Hence, we present size distributions of pooled flat ACF and tumors to illustrate the effects of the dietary interventions (Fig 2). As expected, Hemin, or Hemin+Nitrite caused a shift towards smaller lesion sizes and fewer lesions compared with Nitrite or Control (Fig 2A). This suppressive effect was apparently due to the presence of hemin in the diet, as illustrated by the size distributions (Fig 2B) of these lesions in mice fed Hemin+ (pooled Hemin and Hemin+Nitrite) compared with mice fed Hemin- (pooled Nitrite and Control). The Two-Way ANOVA (Table 2) showed that hemin in the diet (Hemin+) caused a statistically significant reduction in the formation of flat ACF and tumors as well as in the growth of flat ACF. Typically, the load of flat ACF and tumors was reduced by approximately 60% (p<0.001 and p = 0.019, respectively). When comparing mice fed Nitrite+ (pooled Nitrite and Hemin+Nitrite) to mice fed Nitrite- (pooled Control and Hemin), no significant difference was observed (Table 2), indicating that nitrite in the diet did not have an effect in the colon of the A/J Min/+ mice.

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