EVIDENCE THAT IRON OVERLOAD PROMOTES 7,12-DIMETHYLBENZ(A)ANTHRACENE-INDUCED SKIN TUMORIGENESIS IN MICE

iron overload is known to occur in West European and American populati ons due to the consumption of an iron-rich diet. There are also geneti c disorders which lead to body iron overload. It has been shown that i ron overload predisposes humans to an increased risk of cancer. In exp erimental animals, iron overload is known to enhance intestinal, colon , hepatic, pulmonary and mammary carcinogenesis. However, the mechanis m by which iron overload enhances chemically-induced carcinogenesis is not known. In this study, we show that iron overload acts as a mild t umor promoter in mouse skin. Female albino swiss mice were given 1 mg iron/mouse parenterally for 2 weeks to induce iron overload. These ani mals showed a three-fold increase in cutaneous iron concentration as c ompared to normal mice. Tumors were initiated by topically applying 7, 12-dimethylbenz(a)anthracene (DMBA). Appearance of the first tumor (la tency period), percent tumor incidence and number of tumors/mouse were recorded. When compared to the control group, iron overload mice show ed an increased incidence of tumors, from 25%-55% by week 20, and tumo rs appeared 4 weeks earlier. The number of tumors per mouse was four-f old higher in the iron overload group. The induction of cutaneous orni thine decarboxylase (ODC) activity and [H-3]thymidine incorporation in cutaneous DNA were higher in iron overload groups as compared to norm al control animals. Similar to other oxidant tumor promoters, iron ove rload enhanced cutaneous lipid peroxidation and xanthine oxidase activ ity and decreased catalase activity. Our results indicate that iron ov erload exerts a mild tumor promoting activity in mouse skin. Our data also show that oxidative stress generated by iron overload plays an im portant role in the augmentation of cutaneous tumorigenesis. These dat a may also have implications for the enhanced risk of cancer-induction following UVB exposure of human populations with iron overload.