Low iron state is associated with reduced tumor promotion in a two-stage mouse skin carcinogenesis model.
The purpose of this study was to investigate the effect of low iron state in a two-stage mouse skin carcinogenesis model using 7,12-dimethylbenz[a]anthracene (DMBA)-initiated and benzoyl peroxide (BPO)-promoted cutaneous tumorigenesis. All mice were treated with DMBA. Low iron state was achieved by injection with phenylhydrazine hydrochloride and feeding low iron diet. A low iron state resulted in a decrease in tumor incidence (papillomas and carcinomas) and number of tumors/mouse. Also, the conversion of papillomas to carcinomas was lower in mice on a low iron state. BPO treatment enhanced epidermal lipid peroxidation (LPO) and was accompanied by a depletion in the level of epidermal reduced glutathione (GSH) and decrease in the activities of antioxidant enzymes. BPO treatment also increased ornithine decarboxylase (ODC) activity and [3H]thymidine incorporation into cutaneous DNA. Mice in a low iron state were less susceptible to the effects of BPO treatment, as was apparent from a partial recovery of GSH levels and the activities of antioxidant enzymes, as well as a lower induction in ODC activity, [3H]thymidine incorporation into cutaneous DNA and lesser epidermal LPO. As expected, cutaneous iron levels were lower in mice on a low iron state. Thus, our data show that the tumor-promoting potential of BPO is reduced by low iron state in a two-stage mouse skin carcinogenesis model.
Bhasin
G
G
Department of Medical Elementology and Toxicology, Hamdard University, New Delhi 110062, India.
Kauser
H
H
Athar
M
M
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D001585:Benzoyl Peroxide / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity*; D002277:Carcinoma / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000378:metabolism; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D015994:Incidence; D007501:Iron / Q000008:administration & dosage / Q000097:blood*; D019266:Iron, Dietary / Q000008:administration & dosage; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D009955:Ornithine Decarboxylase / Q000187:drug effects / Q000378:metabolism; D010212:Papilloma / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism*
D002273:Carcinogens; D004273:DNA, Neoplasm; D019266:Iron, Dietary; D015127:9,10-Dimethyl-1,2-benzanthracene; D007501:Iron; D009955:Ornithine Decarboxylase; D005978:Glutathione; D001585:Benzoyl Peroxide