Genotoxic effects of some l-[(benzofuran-2-yl)-phenylmethyl]-imidazoles on MCF-7 cell line

Abstract

Increased exposure to estrogen has been associated with the risk of breast cancer. Substituted benzofuran derivatives with inhibitory effects on estrogen synthesis could be considered as a potential approach to reduce the risk of breast cancer. The study of cytotoxic effects of these compounds has suggested involvement of other mechanisms such as DNA damage. In the current study we have investigated genotoxic effects of some benzofuran derivatives on MCF-7 cell line. The MCF-7 cell line was exposed both to benzofuran phenylmethyl imidazole and its 4- fluoro, 4-chloro, 2-methoxy and 2-methyl derivatives for 2 h. The Comet assay was used to examine DNA damage due to this exposure. We also studied the DNA repair capacity after 2 h exposure to genotoxic concentrations of these compounds and their recovery were evaluated after 17 and 24 h, using the comet assay. The results indicated that genotoxic effects of these compounds appeared in concentrations of 10^-8 to 10^-6 M. The 4- fluoro and 4-chloro derivatives exhibited the highest genotoxicity and the unsubstituted benzofuran phenylmethyl imidazole had the lowest effect. The 4- fluoro, 4-chloro and 2-methyl derivatives were recovered after 24 h while 2-methoxy and the unsubstituted derivatives were recovered after 17 h. The results showed that these compounds are genotoxic and the concentration of tested benzofuran derivatives with genotoxic effects are not close to their enzyme inhibitory concentration. Moreover, our study shows that the DNA damages are repairable. Therefore, it seems that the investigated compounds have the potentials as therapeutic agents.