Document Detail

Dietary iron promotes azoxymethane-induced colon tumors in mice.
MedLine Citation:
PMID:  15489209     Owner:  NLM     Status:  MEDLINE    
There is accumulating evidence that high levels of dietary iron may play a role in colon carcinogenesis. We used a mouse model to investigate the impact of elevated dietary iron on incidence of aberrant crypt foci (ACF; a preneoplastic lesion) on tumor formation and on induction of oxidative stress. A/J mice were injected intraperitoneally, once a week for 6 weeks, with the colonotropic carcinogen, azoxymethane (AOM) or saline (vehicle controls). Following AOM or saline treatments, mice were placed on diets of high (3,000 ppm) and low (30 ppm) iron. Mice in each treatment group were sacrificed at 6 and 10 weeks following the final injection with AOM or saline. Colons were removed for subsequent histopathological analysis, which revealed average increases of 4.6 +- 1.3 vs. 10.4 +- 2.5 total tumors at 6 weeks and 30.75 +- 2.7 vs. 41.5 +- 4.4 total tumors at 10 weeks per AOM-treated mouse on low- and high-iron diets, respectively. There were no significant differences in incidence of ACF attributable to iron, although there was a trend toward greater crypt multiplicity per focus in mice on high-iron diets. Notably, no tumors were observed in mice receiving vehicle control injections in place of carcinogen, regardless of the level of dietary iron. These data suggest that iron exerts its effect at the stage of tumor promotion, but is not sufficient to initiate tumor formation. To learn more about mechanisms by which iron promotes tumor growth, colons were assayed for several biomarkers of oxidative stress [BOS; total F2-isoprostanes (F2-IsoPs), 15-F2t-isoprostanes (8-IsoPGF2s), Isofurans (IsoFs), and 8-hydroxyguanosines (8-OH[d]Gs)], as well as iron absorption, programmed cell death, and cellular proliferation. Elevated PCNA and TUNEL staining of the colon epithelium revealed hyperproliferative and apoptotic responses to iron, while no significant differences between iron groups were observed in each of the BOS that were assayed. Our results suggest that, following carcinogen exposure, elevated dietary iron promotes the growth of tumors with altered cellular homeostasis through a mechanism that is independent of oxidative stress.
Jillian N M Ilsley; Glenn S Belinsky; Kishore Guda; Qi Zhang; Xi Huang; Jeffrey B Blumberg; Paul E Milbury; L Jackson Roberts; Richard G Stevens; Daniel W Rosenberg
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Nutrition and cancer     Volume:  49     ISSN:  0163-5581     ISO Abbreviation:  Nutr Cancer     Publication Date:  2004  
Date Detail:
Created Date:  2004-10-18     Completed Date:  2005-04-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7905040     Medline TA:  Nutr Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  162-9     Citation Subset:  IM    
Center for Molecular Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA.
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MeSH Terms
Apoptosis / drug effects
Azoxymethane / toxicity
Carcinogens / toxicity
Cell Division / drug effects
Colonic Neoplasms / chemically induced,  etiology*,  pathology
DNA Damage / drug effects
Disease Models, Animal
Dose-Response Relationship, Drug
In Situ Nick-End Labeling
Iron, Dietary / pharmacology*
Oxidative Stress / drug effects*
Precancerous Conditions / chemically induced,  etiology,  pathology
Random Allocation
Time Factors
Grant Support
Reg. No./Substance:
0/Carcinogens; 0/Iron, Dietary; 25843-45-2/Azoxymethane

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