Sodium arsenite enhances copper accumulation in human lung adenocarcinoma cells

In this report, we found that arsenite-resistant human lung adenocarcinoma cells, CL3R15, were more susceptible to CuCl2 than the parental CL3 cells. With the aid of atomic absorption spectrophotometry, we observed that CL3R1 5 cells accumulated more copper than CL3 cells. We further demonstrated tha t sodium arsenite treatment resulted in a dose-dependent increase of copper accumulation in the parental CL3 cells. In contrast, copper did not alter the levels of intracellular arsenite in CL3 cells treated in combination wi th sodium arsenite and CuCl2. Pretreatment of CL3 cells with sodium arsenit e resulted in a significant increase of copper accumulation and cytotoxicit y, These results indicate that intracellular copper accumulation is enhance d by arsenite, However, arsenite-enhanced copper accumulation was not obser ved in two fibroblastic cells, GM00220 and GM03700, derived from Menkes pat ients. The Menkes gene encodes a membrane pump responsible for copper expor tation. Our results suggest that Menkes protein is a potential target of ar senite.