Journal of Clinical Toxicology
Open Access

Abstract

Differential Effects of Organic and Inorganic Mercury on Phenotypically Variant Breast Cancer Cell Lines

David R Wallace and Eric Bates

Mercury remains a major environmental contaminant world-wide. Increasing evidence supports heavy metals as estrogenic agents (metalloestrogens), yet the impact of organic and inorganic mercury is unclear. The intent of this study was to increase understanding of mercury compounds as tumor causing agents and their modes of action. Changes in cellular viability, proliferation, and apoptosis after exposure to inorganic (HgCl2) and organic (CH3Hg+) mercury, were examined using a control human breast epithelial cell line (MCF-12A) compared to the human breast cancer cell lines, MCF-7 (ER+) and MDA-MB-453 (ER-). Exposure to mercuric compounds increased cellular proliferation (2-fold), altered caspase activity and p53 expression in a compound dependent manner in MCF-12A cells. Between the two tumor lines, MDA-MB-453 cells appeared most like MCF-12A cells with regard to the mercury response. MCF-7 (ER+) cells on the other hand, were relatively resistant to the effect of both HgCl2 and CH3Hg+ as indicated by the relative lack of change in any of the parameters measured. The proliferation and viability of MCF-7 cells was not significantly affected and although 5 ppm CH3Hg+ significantly increased caspase activity, there was a net inhibition of p53 expression at the same concentration. Collectively, MCF-12A (normal epithelial) cells were most sensitive to both HgCl2 and CH3Hg+. Cellular adaption and activation of the p53/apoptosis pathway would minimize tumorigenesis which was dependent on the chemical form of mercury. These protective effects were not observed in the tumor cell lines with the MCF-7 (ER+) cells being the most resistant to the mercury effects. A significant difference between MCF-7 and MDA-MB-453 cells is expression of the estrogen receptor, suggesting potential involvement of this receptor in the effects of mercuric compounds. Further work is necessary to examine the potential role of the estrogen receptor in modulating the effects of mercuric compounds on tumor development.