Organochlorine compounds (OCs) are a group of persistent chemicals that accumulate in fatty tissues with age. Although OCs has been tested individually for their capacity to induce
breast cancer cell proliferation, few studies examined the effect of
complex mixtures that comprise compounds frequently detected in the serum of women. We constituted such an OC mixture containing 15 different components in environmentally relevant proportions and assessed its proliferative effects in four
breast cancer cell lines (MCF-7, T47D, CAMA-1, MDAMB231) and in non-cancerous
CV-1 cells. We also determined the capacity of the mixture to modulate cell cycle stage of
breast cancer cells and to induce estrogenic and antiandrogenic effects using gene reporter assays. We observed that low concentrations of the mixture (100 × 10(3) and 50 × 10(3) dilutions) stimulated the proliferation of MCF-7 cells while higher concentrations (10 × 10(3) and 5 × 10(3) dilutions) had the opposite effect. In contrast, the mixture inhibited the proliferation of non-
hormone-dependent cell lines. The mixture significantly increased the number of MCF-7 cells entering the S phase, an effect that was blocked by the
antiestrogen ICI 182,780. Low concentrations of the mixture also caused an increase in CAMA-1 cell proliferation but only in the presence
estradiol and
dihydrotestosterone (p<0.05 at the 50 × 10(3) dilution).
DDT analogs and
polychlorinated biphenyls all had the capacity to stimulate the proliferation of CAMA-1 cells in the presence of sex
steroids. Reporter gene assays further revealed that the mixture and several of its constituents (
DDT analogs,
aldrin,
dieldrin, β-
hexachlorocyclohexane,
toxaphene) induced
estrogenic effects, whereas the mixture and several components (
DDT analogs,
aldrin,
dieldrin and
PCBs) inhibited the
androgen signaling pathway. Our results indicate that the complex OC mixture increases the proliferation of MCF-7 cells due to its estrogenic potential. The proliferative effect of the mixture on CAMA-1 cells in the presence of sex
steroids appears mostly due to the antiandrogenic properties of
p,p'-DDE, a major constituent of the mixture. Other mixtures of contaminants that include emerging compounds of interest such as brominated
flame retardants and perfluoroalkyl compounds should be tested for their capacity to induce
breast cancer cell proliferation.