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elevated dietary iron promotes the growth of tumors
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Nutr Cancer. 2004;49(2):162-9. Links

Dietary iron promotes azoxymethane-induced colon tumors in mice.

Ilsley JN, Leung SF, Belinsky GS, Guda K, Zhang Q, Huang X, Blumberg JB,
Milbury PE, Roberts Ii LJ, Stevens RG, Rosenberg DW.

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.

PMID: 15489209 [PubMed - in process]

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