Accumulation of promutagenic DNA adducts in the mouse distal colon after consumption of heme does not induce colonic neoplasms in the western diet model of spontaneous colorectal cancer.

Abstract

SCOPE:

Red meat is considered a risk factor for colorectal cancer (CRC). Heme is considered to promote colonic hyperproliferation and cell damage. Resistant starch (RS) is a food that ferments in the colon with studies demonstrating protective effects against CRC. By utilizing the western diet model of spontaneous CRC, we determined if feeding heme (as hemin chloride) equivalent to a high red meat diet would increase colonic DNA adducts and CRC and whether RS could abrogate such effects.

METHODS AND RESULTS:

Four groups of mice: control, heme, RS and heme + RS were fed diets for 1 or 18 months. Colons were analyzed for apoptosis, proliferation, DNA adducts "8-hydroxy-2-deoxyguanosine" and "O(6) -methyl-2-deoxyguanosine" (O(6) MeG), and neoplasms. In the short term, heme increased cell proliferation (p < 0.05). Changes from 1 to 18 months showed increased cell proliferation (p < 0.01) and 8-hydroxy-2-deoxyguanosine adducts (p < 0.05) in all groups, but only heme-fed mice showed reduced apoptosis (p < 0.01) and increased O(6) MeG adducts (p < 0.01). The incidence of colon neoplasms was not different between any interventions.

CONCLUSION:

We identified heme to increase proliferation in the short term, inhibit apoptosis over the long term, and increase O(6) MeG adducts in the colon over time although these changes did not affect colonic neoplasms within this mouse model.

• Authors: Jean Winter, Graeme P Young, Ying Hu, Silvia W Gratz, Michael A Conlon, Richard K Le Leu
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 58 Issue 3 Pg. 550-8 (Mar 2014) ISSN: 1613-4133 [Electronic] Germany
• PMID: 24115497 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• DNA Adducts
• Mutagens
• Heme
• Starch

Topics

• Animals
• Body Weight (drug effects)
• Colonic Neoplasms (etiology, pathology)
• Colorectal Neoplasms (etiology)
• DNA Adducts (metabolism)
• Diet, Western (adverse effects)
• Feces
• Heme (adverse effects)
• Humans
• Male
• Mice, Inbred C57BL
• Mutagens (metabolism)
• Starch (pharmacology)