Hormesis Effect of Trace Metals on Cultured Normal and Immortal Human Mammary Cells
Frank A. Barile, Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences
R. Konsoula, Graduate Student
C.M. Schmidt, C.N. Cheng, and A. Marino, Undergraduate Students
An in vitro study was conducted to determine the effects of variable concentrations of trace metals on human cultured mammary cells. Monolayers of human mortal (MCF-12A) and immortal (MDA-MB231) mammary epithelial cells were incubated in the absence or presence of increasing concentrations of arsenic (As), mercury (Hg) and copper (Cu) for 24-h, 72-h, 4-d, and 7-d. The MTT assay was used to assess viability. Monolayers were also labeled with rhodamine-110 (R-6501), Sytox green®, and Celltiter blue™ fluorescent dyes as indicators for intracellular esterase activity, nucleic acid staining, and cell reduction/viability, respectively. The data suggest that there is a consistent protective and/or stimulating effect of metals at the lowest concentrations in MCF-12A cells that is not observed in immortal MDA-MB231 cells. In fact, cell viability of MCF-12A cells is stimulated by otherwise equivalent inhibitory concentrations of As, Cu, and Hg on MDA-MB231 cells at 24-h. Whereas As and Hg suppress proliferation and viability in both cell lines after 4-d and 7-d of exposure, Cu enhances cell proliferation and viability of MCF-12A cells. MDA-MB231, however, recover better after 4-days of toxic insult. The study demonstrates that a hormesis effect from trace metals is detectable in cultured mammary cells. In addition, sensitivity of mammary cells to lower concentrations of Cu, a biologically important trace metal, may play an important role in controlling cellular processes and proliferation. (Supported by NIH/NIEHS/AREA R15 ES012170-01).