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
Date
2013-10-01
Authors
Winter, Jean
Young, Graeme Paul
Hu, Ying
Gratz, Silvia W
Conlon, Michael A
Le Leu, Richard Kevin
Journal Title
Journal ISSN
Volume Title
Publisher
Wiley-Blackwell
Rights
WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Rights Holder
(C) 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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 increasedO6MeGadducts
(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.
Description
Author version made available in accordance with Publisher copyright policy.
Keywords
Cancer research, Nutrition and health, Heme
Citation
Winter, J., Young, G.P., Hu, Y., Gratz, S.W., Conlon, M.A. and Le Leu, R.K., 2013. 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. Molecular Nutrition and Food Research, doi: 10.1002/mnfr.201300430.