IRON OVERLOAD AUGMENTS 7,12-DIMETHYL-BENZ(A)ANTHRACENE-INITIATED AND 12-O-TETRADECANOYLPHORBOL-13-ACETATE-PROMOTED SKIN TUMORIGENESIS

Reactive oxygen species and free radicals have been implicated in the multistep cutaneous chemical carcinogenesis. Much of the experimental evidence in this regard is indirect and is based on observations that prooxidant status usually enhances and antioxidant treatments generall y inhibit tumor yield, Iron overload is known to enhance peroxidative damage and cause oxidative stress. In this study, we report that iron overload augments 12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated cutaneous tumor promotion, Female Swiss mice were subjected to iron ov erload by injecting I mg iron/ mouse/day consecutively for 2 weeks. Tu mors were initiated by applying a single dose of 7,12-dimethylbenz(a)a nthracene and promoted with twice weekly applications of TPA for 20 we eks and the appearance of first tumor (latency period), percent incide nce and number of tumors per mouse were recorded. It has been observed that the level of iron in involved (tumor-bearing) skin was about fou rfold higher as compared to uninvolved (non-tumor) skin of iron overlo ad animals and about tenfold higher as compared to the iron level in t he skin of normal animals. When compared to the iron-unloaded control group, the iron overload mice showed an increased incidence of tumors, In iron overload animals, the tumors appeared 3 weeks earlier and als o the number of tumors per mouse was significantly higher (2.5-fold), These data indicate that iron overload augments TPA-mediated tumor pro motion. We propose that oxidative stress generated by iron overload ma y be responsible for the augmentation of cutaneous tumorigenesis.