EFFECT OF IRON OVERLOAD ON 7, 12-DIMETHYLBENZ (A) ANTHRACENE-INDUCED SKIN TUMORIGENESIS

Iron overload is known to occur in the West European and American population due to the consumption of iron-rich diets. On the other hand, genetic disorders leading to iron overload are also known. Iron overload leads to increased peroxidation and disruptive disintegration of lipid-rich membranes, and predisposes humans for an enhanced risk of cancer induction. In experimental animals iron overload enhances intestinal, colonic, hepatic, pulmonary and mammary carcinogenesis. In this study, we have shown that iron overload is a mild tumor promotor in mouse skin. Female albino Swiss mice were iron overloaded and their backs were shaved. Tumors were initiated using a complete tumorigenesis protocol by applying 200lig 7, 12-dimethylbenz (a) anthracene (DMBA)/mouse in multiple doses of 40llg DMBA/day for 5 consecutive days. The appearance of the first tumor (latency period), percent of tumor incidence and number of tumors/ mouse were recorded. When compared to the positive control group, the iron overloaded mice showed an increased incidence of tumors. In iron overloaded animals, the tumors appeared about four weeks earlier. The number of tumors per mouse were significantly higher in the iron overloaded group. Biochemical studies performed in the present study include the determination of the activity of lipid peroxidation, catalase and xanthine oxidase measurement in mice skin tissue. We observed an iron-mediated induction in lipid peroxidation (LPO) and xanthine oxidase (XOD) and diminished catalase (CAT) activity in skin tissues of mice overloaded with iron as compared to the normal unloaded control group. Based on these studies we propose that iron increases tumor promotion potentials significantly. An induction in LPO in the iron overloaded group suggests that oxidative stress may be responsible for such an observed augmentation of cutaneous carcinogenesis in mice. Our data indicate that iron overload exerts tumor promoting potential in mouse skin, and that oxidative stress generated by iron overload is responsible for the augmentation of cutaneous tumorigenesis