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

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