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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

Authors

  • Jean Winter,

    Corresponding author
    1. Flinders Centre for Innovation in Cancer, Flinders University, Adelaide, South Australia, Australia
    • Correspondence: Dr. Jean Winter, Flinders Centre for Innovation in Cancer, Flinders University, Adelaide, South Australia, Australia

      E-mail: jean.winter@flinders.edu.au

      Fax: +618-8204-5703

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  • Graeme P. Young,

    1. Flinders Centre for Innovation in Cancer, Flinders University, Adelaide, South Australia, Australia
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  • Ying Hu,

    1. Flinders Centre for Innovation in Cancer, Flinders University, Adelaide, South Australia, Australia
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  • Silvia W. Gratz,

    1. Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, United Kingdom
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  • Michael A. Conlon,

    1. Preventative Health National Research Flagship, CSIRO and CSIRO Animal Food and Health Sciences, Adelaide, South Australia, Australia
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  • Richard K. Le Leu

    1. Flinders Centre for Innovation in Cancer, Flinders University, Adelaide, South Australia, Australia
    2. Preventative Health National Research Flagship, CSIRO and CSIRO Animal Food and Health Sciences, Adelaide, South Australia, Australia
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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.

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