Low iron diet retards tumor promotion .

Arch Toxicol. 2004 May;78(5):283-9. Epub 2004 Mar 3. Related Articles,
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Low iron diet retards 12-O-tetradecanoyl phorbol-13-acetate-mediated
tumor promotion in murine skin.

Bhasin G, Kauser H, Athar M.

Department of Medical Elementology and Toxicology, Faculty of Science,
Hamdard University, 110062, New Delhi, India.

Recently, we have shown that low iron state reduces benzoyl
peroxide-mediated tumor promotion in murine skin. To further test the
dependence of iron on skin tumor development, we assessed the effect of
a low iron diet on 12- O-tetradecanoyl phorbol-13-acetate
(TPA)-mediated tumor promotion in murine skin. Female Swiss albino mice
were fed on a low iron diet and initiated with a single dose of
7,12-dimethylbenz[ a]anthracene (DMBA, 40 microg as 150 microl per
mouse) and promoted with TPA (2.5 microg as 200 microl per mouse,
twice-weekly application for 20 weeks). The appearance of the first
papilloma and the number of tumors (papillomas and carcinomas) per
mouse were recorded weekly. We observed a decrease in tumor incidence
(papillomas and carcinomas) and number of tumors per mouse in
TPA-promoted mice fed on low iron diet (0.23 mg Fe/kg diet) compared to
normal mice fed on balanced mouse chow (1.70 mg Fe/kg diet). The total
iron consumption per day by mice being fed on balanced mouse chow was
340-400 microg Fe/kg body weight, and the total iron consumption per
day by mice being fed on low iron diet was 45-55 microg Fe/kg body
weight. The number of papillomas per mouse was 45% lower and the
conversion of papillomas to carcinomas was about 20% lower in mice fed
a low iron diet. The tumor size was also smaller in mice being fed on
low iron diet. TPA treatment resulted in decreases in the activities of
antioxidant enzymes and depletion in the level of epidermal reduced
glutathione (GSH). Feeding mice on low iron diet along with TPA
treatment resulted in approximately 50-75% recovery of the depleted
levels of GSH and antioxidant enzymes. In addition, TPA-mediated
induction of biological markers of tumor promotion, viz. ornithine
decarboxylase activity and [(3)H]thymidine incorporation into cutaneous
DNA, was about 60% lower in TPA-treated mice fed on low iron diet than
in normal mice treated with TPA. Cutaneous iron levels were also lower
in mice fed on low iron diet than in mice fed on normal diet.
Histopathological sections of the skin portion adjoining tumors showed
a lower degree of epidermal hyperplasia and lesser infiltration of
inflammatory cells in the dermis, and absence of hyperkeratosis in mice
fed on low iron diet. Thus, in this study we observe that the tumor
promoting potential of TPA is reduced in mice fed on low iron diet,
which is also accompanied by lesser inflammatory changes in the skin of
tumor-bearing mice fed on low iron diet.

PMID: 14997284 [PubMed - indexed for MEDLINE]


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