Evidence that iron overload plus croton oil induce skin tumours in mice

Iron overload is known to occur due to different factors including genetic disorders. It has been shown that iron overload predisposes humans to an increased risk of cancer. However, the mechanism by which iron overload enhances chemically induced carcinogenesis is not known. In this report, for the first time it is shown that iron overload acts as a tumour initiator. Female albino Swiss mice were given iron dextran 1 mg/mouse per day intramuscularly for 15 days and croton oil 0.5 mg in 200 microL acetone/mouse topically twice a week for 30 weeks. During this period, the animals were observed for tumour incidence. There were significantly higher yields of tumours in those animals receiving both iron and croton oil. However, the group of animals treated only with acetone, iron, croton oil and 7,12-dimethylbenz(a)anthracene (DMBA) alone did not develop any tumours during 30 weeks of observation. Further, croton oil-mediated induction in cutaneous lipid peroxidation (LPO) level was higher in the iron-overload group. The results of this study suggest that oxidative stress generated by iron overload is responsible for croton oil-mediated skin carcinogenesis.