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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 micro g as150 micro l
per mouse) and promoted with TPA (2.5 micro g as 200 micro l
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 micro g Fe/kg body weight,
and the total iron consumption per day by mice being fed on
low iron diet was 45-55 micro g 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 ~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 - as supplied by publisher]
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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 micro g as150 micro l
per mouse) and promoted with TPA (2.5 micro g as 200 micro l
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 micro g Fe/kg body weight,
and the total iron consumption per day by mice being fed on
low iron diet was 45-55 micro g 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 ~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 - as supplied by publisher]
------------------------------------------------------------
--------------
------
Who loves ya. Tom Jesus Was A Vegetarian!
http://jesuswasavegetarian.7h.com Man Is A Herbivore!
http://pages.ivillage.com/ironjustice/manisaherbivore DEAD
PEOPLE WALKING
http://pages.ivillage.com/ironjustice/deadpeoplewalking