role of nitric oxide and metallothionein in cytotoxic activity of cadmium in caco-2 cells

Cadmium (cd) induces carcinogenicity and cytotoxicity through a variety of mechanisms. metallothioneins (mts) play critical roles in metal detoxification and radical scavenging. here we evaluated the possible involvement of no and mt in cd-induced toxicity and resistance development. by utilizing cd-resistant caco-2 cells as a model of chronic exposure to cadmium, we observed that cd decreased caco-2 cell proliferation, whereas cd-resistant cells showed a lower sensitivity to cd cytotoxicity. l-name as an inos inhibitor and cptio as an no scavenger induced a significant reduction in cd-mediated toxicity of parent caco-2 in spite of resistant cells. in resistant cells, inos mrna expression was declined; however, mt protein synthesis was increased following acute and chronic cd exposure. it seems that no synthesis involves in cd-induced cytotoxicity, while elevated mt expression is associated with cd detoxification and resistance.