Effect of iron overload on the benzoyl peroxide-mediated tumor promotion in mouse skin

Rezazadeh, Hassan; Athar, Mohammad

doi:10.1016/s0304-3835(97)00512-0

Cited by 18 publications

(10 citation statements)

References 17 publications

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“…Dose regimen and treatment protocols are described in the text 215±12* 36±3** 52±4** 89±9* 70±4*** *p<0.05, **p<0.01, ***p<0.001, significantly different: TPA-treated group compared with acetone-treated group; TPA (low iron diet)-treated group compared with TPA-treated group response is augmented by porphyrin photosensitization of DMBA-initiated murine skin (Giri et al 1999). Similarly, iron catalyses the production of hydroxyl radicals from hydrogen peroxide via the Fenton reaction (Conrad et al 1999), which are highly clastogenic, as observed in our earlier studies (Razazadeh et al 1997;Razazadeh and Athar 1998;Bhasin et al 2002Bhasin et al , 2003. It has been reported that excess of intracellular iron augments TPA-mediated skin tumor promotion (Razazadeh et al 1997).…”

Section: Discussionsupporting

confidence: 63%

“…Iron consumption has been associated with incidence of colorectal cancer (Nelson 2001). We have shown that iron-overload enhances the tumor promoting potency of 12-O-tetradecanoyl phorbol-13-acetate (TPA) and benzoyl peroxide (BPO) in murine skin (Razazadeh et al 1997;Razazadeh and Athar 1998). Recently, we have also shown that even small doses of iron can augment TPA/BPO-mediated tumor promotion in murine skin (Bhasin et al 2003).…”

Section: Introductionmentioning

confidence: 99%

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Low iron diet retards 12- O -tetradecanoyl phorbol-13-acetate-mediated tumor promotion in murine skin

Bhasin

Kauser

Athar

2004

Archives of Toxicology

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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.

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Section: Discussionsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Low iron diet retards 12- O -tetradecanoyl phorbol-13-acetate-mediated tumor promotion in murine skin

Bhasin

Kauser

Athar

2004

Archives of Toxicology

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“…The mechanism of iron contributing to carcinogenesis has not been determined. Possible mechanisms include the important role of iron in the production of free oxygen radicals [37], causing secondary damage to nucleic acids [38], thereby inducing [39] and promoting [40][41][42] carcinogenesis. Various iron chelators have antiproliferative activity on hepatoma cell lines [43][44][45][46].…”

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confidence: 99%

Trace Element Concentration in Primary Liver Cancers—A Systematic Review

Gurusamy

2007

Biol Trace Elem Res

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“…Cell malignant transformation induced by oxidative stress has been shown to be mediated by intracellular iron (Nassi-Calo et al 1989). In our laboratory we have shown that ironoverload enhances benzoyl peroxide (BPO, free radical generator)-mediated cutaneous tumor promotion (Razazadeh and Athar 1998). Similarly, we have shown that iron-overload enhances TPA-mediated cutaneous tumor promotion (Razazadeh et al 1997).…”

Section: Introductionmentioning

confidence: 79%

Free radical generating agents lead to the rapid progression of benign skin tumors to carcinoma in iron-overloaded mice

Bhasin

Kauser

Athar

2004

Archives of Toxicology

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Free radical generating compounds have been shown to enhance the malignant conversion of papillomas to carcinomas in mouse skin, and iron has been shown to participate in free radical generating reactions. In the present study, we investigated whether iron can play a role in the malignant conversion of papillomas to carcinomas. Skin tumors were chemically induced in female Swiss albino mice using a standard two-stage initiation-promotion protocol. Topical application of 12- O-tetradecanoyl phorbol 13-acetate (TPA), benzoyl peroxide (BPO), H(2)O(2) and cumene hydroperoxide (COOH) to these tumor-bearing mice increased the rate of malignant conversion. To evaluate the effect of iron-overload on the conversion of benign skin papillomas to carcinomas, the animals were pre-treated with 1.0 mg Fe per mouse for 15 days before they received TPA or free radical generating compounds. The number of carcinomas and the percent incidence of carcinomas were recorded weekly. The rate of malignant conversion was higher in iron-overloaded mice as compared with non-iron-overloaded mice. The ability of iron-overload in enhancing the malignant conversion was in the order TPA

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Effect of iron overload on the benzoyl peroxide-mediated tumor promotion in mouse skin

Cited by 18 publications

References 17 publications

Low iron diet retards 12- O -tetradecanoyl phorbol-13-acetate-mediated tumor promotion in murine skin

Low iron diet retards 12- O -tetradecanoyl phorbol-13-acetate-mediated tumor promotion in murine skin

Trace Element Concentration in Primary Liver Cancers—A Systematic Review

Free radical generating agents lead to the rapid progression of benign skin tumors to carcinoma in iron-overloaded mice

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