LIMITATIONS OF THE MCF-7 CELL-PROLIFERATION ASSAY FOR DETECTING XENOBIOTIC ESTROGENS

The MCF-7 cell assay has recently been proposed as a primary screen fo r the detection of xenobiotic oestrogens. The assay is based on the ab ility 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 w ith this assay. There was significant variability between experiments in the response of MCF-7 cells to oestradiol, from twofold to sevenfol d increases, sometimes with no evidence of a dose response. The backgr ound rate of cell proliferation (in the absence of oestradiol) also va ried between experiments, from a low basal rate in some experiments to rates approaching that of oestradiol-treated cells in others. The var iability in our experiments may be due to selection of sub-clones of c ells at passage. We also determined the effects of oestrogens on the n on-oestrogen responsive human breast cancer cell line MDA-MB-231. Thes e cells did not proliferate in response to oestradiol, but nonylphenol promoted a two-to threefold increase in cell number. Our data illustr ate the potentially unpredictable nature of breast cancer cell lines w hen used routinely as a screening test for xenobiotic oestrogens. (C) 1998 Elsevier Science Ltd. All rights reserved.