Study on the effects of Feric nitrilotriacetate on 7, 12-Dimethylbez (a) anthracene and coroton oil induced skin tumorigenesis in the mice

Abstract

Cancer incidence is one of the human problems and in order to understand its mechanistic aspects several studies have been performed. Ferric nitrilotriacetete¬(Fe-NTA) causes tumors in the kidney. Objective: The purpose of this study was to investigate the carcinogenesis effect of Fe-NTA in mice skin. Methods¬&¬Materials: Albino Swiss mice were divided into 4 groups and the back of the mice were shaved. After 24 hours, the animals of groups 2,¬3,¬4 received 3¬doses of 6,¬9 and 12 mg of Fe-NTA topically for 15 days. Fe-NTA was applied before using Dimethylbenz(a)anthracene (DMBA). After 24 hours, the mice of all groups were initiated by a single dose of DMBA. After 7 days, animals were promoted topically by croton oil¬(cr.oil) twice weekly for period of 28¬weeks. Results: At the end of 9th week the first tumors were observed in the group of animals receiving ferric nitrilotriacetete 12¬mg, plus DMBA and promoted with croton oil. However in the control group, the tumor occurred at end of week 14th. Also both number and percentage of tumor incidence significantly were higher in group receiving Fe-NTA 12¬mg at various intervals of times. Further, in the tumor tissues the level of iron was higher in Fe-NTA¬(12 mg) treated animals. The results of this study may suggest that oxidative stress generated by iron overload is responsible for the croton oil-mediated skin carcinogenesis.

Discussion: The results obtained from this study showed that higher dose of Fe-NTA could exacerbate skin tumors in comparison to the control group. Overall, our study demonstrates that Fe-NTA in its high dose is responsible for mouse skin carcinogenesis. The role of excessive doses of Fe-NTA in mice skin induction may be due to its potential capabilities of producing oxidative injuries and DNA damage.