The role of nitric oxide synthase in an early phase Cd-induced acute cytotoxicity in MCF-7 cells.

Literature to date has confirmed that cadmium (Cd) can accomplish its toxic effects via the free radical-induced damage, but Cd itself cannot generate free radicals directly. Nitric oxide (NO) is a fundamental molecule that interplays with reactive oxygen species (ROS), which may be associated with the Cd-induced cytotoxicity. However, the role of nitric oxide synthase (NOS) in an early phase Cd-induced acute cytotoxicity and its interaction has not been studied. In this report, we provide data showing that CdCl2 (10 μM, 100 μM, 1 mM) could modulate NOS activity in terms of NO production which was first suppressed with the release of Ca(2+) and Zn(2+), then induced with the transcriptional and translational activation of the three NOS isoforms in a possible feedback manner. The ROS level in cells was increased after CdCl2 exposure. By using the free radical scavenger N-acetyl-L-cysteine (LNAC) or the NOS activity inhibitor N(G)-methyl-L-arginine (LNMMA), it was demonstrated that NOS played a critical role on the Cd-induced ROS generation. The Cd-induced cytotoxicity was associated with the NOS-mediated oxidative stress in MCF-7 cells.