Limitations of the mcf-7 cell proliferation assay for detecting xenobiotic oestrogens

The MCF-7 cell assay has recently been proposed as a primary screen for the detection of xenobiotic oestrogens. The assay is based on the ability of human breast cancer cells (MCF-7) to proliferate in response to oestrogens. The use of this assay has a number of known drawbacks, such as the differing responses of cells from different sources. This paper describes the sources of variability which we have encountered with this assay. There was significant variability between experiments in the response of MCF-7 cells to oestradiol, from twofold to sevenfold increases, sometimes with no evidence of a dose response. The background rate of cell proliferation (in the absence of oestradiol) also varied between experiments, from a low basal rate in some experiments to rates approaching that of oestradiol-treated cells in others. The variability in our experiments may be due to selection of sub-clones of cells at passage. We also determined the effects of oestrogens on the non-oestrogen responsive human breast cancer cell line MDA-MB-231. These cells did not proliferate in response to oestradiol, but nonylphenol promoted a two- to threefold increase in cell number. Our data illustrate the potentially unpredictable nature of breast cancer cell lines when used routinely as a screening test for xenobiotic oestrogens.