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

Jean Winter, Graeme Young, Ying Hu, Silvia Gratz, Michael Conlon, Richard Le Leu

    Research output: Contribution to journalArticle

    17 Citations (Scopus)

    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 "O6-methyl-2-deoxyguanosine" (O6MeG), 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 O6MeG 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 O6MeG adducts in the colon over time although these changes did not affect colonic neoplasms within this mouse model.

    Original languageEnglish
    Pages (from-to)550-558
    Number of pages9
    JournalMolecular Nutrition and Food Research
    Volume58
    Issue number3
    DOIs
    Publication statusPublished - Mar 2014

    Keywords

    • 8-Hydroxy-2-deoxyguanosine
    • Heme
    • O -Methyl-2-deoxyguanosine
    • Red meat
    • Resistant starch

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