EFFECT OF IRON OVERLOAD ON THE BENZOYL PEROXIDE-MEDIATED TUMOR PROMOTION IN MOUSE SKIN

In this communication, we report that iron overload augments benzoyl p eroxide (BPO)-mediated tumor promotion in 7,12-dimethylbenz[a]anthrace ne (DMBA)-initiated mouse skin. Female albino Swiss mice were overload ed with iron and tumors were initiated by applying a single topical ap plication of DMBA. A week after the initiation, promoting agent, BPO, was applied three times/week for 46 weeks. The appearance of the first tumor (papilloma) and the number of tumors/mouse were recorded. When compared to the control group, the iron-overloaded mice showed an incr eased incidence of tumors at various time intervals. In iron-overloade d animals, tumors appeared earlier and also the number of tumors/mouse was significantly higher. These data could be correlated with the iro n levels of mouse skin in the two groups. Further, BPO-mediated induct ion in ornithine decarboxylase (ODC) activity and [H-3]thymidine incor poration in cutaneous DNA were higher in the iron overload group. In a ddition, in iron-overloaded mice, cutaneous lipid peroxidation (LPO) a nd xanthine oxidase (XOD) activities were higher, whereas catalase act ivity was reduced. Similar to papilloma induction, a significant incre ase in carcinoma yield and incidence was observed in iron-overloaded a nimals. Based on this study, we propose that iron overload significant ly increases the tumor promotion and progression potential of BPO. We suggest that oxidative stress generated by iron overload is responsibl e for the augmentation of BPO-mediated cutaneous tumorigenesis. (C) 19 98 Elsevier Science Ireland Ltd.