The protective role of Nrf2 in cadmium-induced DNA damage

Abstract

Cadmium is mutagenic and carcinogenic metal. Cadmium exposure is known to associate with various types of cancer in human. It has been suggested that cadmium-induced oxidative stress is linked with its cytotoxic effects, a number of studies have supported the role of reactive oxygen species (ROS) in cadmium-induced toxicity. Meanwhile, Nuclear-factor-erythroid 2-related factor 2 (Nrf2) is a member of basic leucine-zipper (bZip) transcription factor family. Particularly, Nrf2 is emerged as a new target for chemoprevention of human environmental carcinogenesis. It has been shown that Nrf2 modulated toxicity of carcinogen by elimination of reactive carcinogenic metabolites. In this study, we examined whether Nrf2 has protective roles against cadmium-induced oxidative stress and genotoxicity. Our experiments were performed with sublethal dose of cadmium that is environmentally relevant concentration in RKO human cell line. We detected significantly high amount of DNA damage in the cadmium treated-Nrf2 lacking RKO as well as increased intracellular ROS generation. Moreover, we found that remarkable induction of micronuclei (MN) that is one of chromosomal damage considered as hallmark of carcinogenicity in cadmiumexposed Nrf2 deficient cells. Therefore, these findings suggested that Nrf2 has important roles in suppression the carcinogenicity of cadmium in terms of protection from oxidative stress-induced DNA damage.