Abstract：The MCF-7cell was used as a research model to evaluate the toxicological effects and estrogenic effects of dibutyl phthalate (DBP) and bisphenol A (BPA). Four analysis methods, including MTT assay, DCFH-DA fluorescent staining, flow cytometry, and real-time fluorescent quantitative PCR (RT-QPCR), were applied to evaluate the effects of DBP and BPA on cell activity (CA), reactive oxygen species (ROS) formation, cell cycle distribution and cell apoptosis, and mRNA transcription levels of three estrogen receptors (e.g., ERα, ERβ and GPR30), respectively. CA represented an inverted U-shape, in which both low dose (10-8mol/L) and high dose (10-4mol/L) exposure to DBP and BPA inhibited cell proliferation but stimulated cell proliferation ranged from 10-7mol/L to 10-5mol/L. The MCF-7cells had the highest cell proliferation rate when exposure concentrations were 10-6mol/L and 10-7mol/L for DBP and BPA, respectively. And the interaction of DBP and BPA was additive action under low-concentration but showed antagonistic effect under high-concentration. On one hand, co-exposure to low-doses DBP and BPA could obviously induce cell proliferation with cell cycle arrest in S phase and mRNA transcription induction of ERα and GPR30; on the other hand, co-exposure to high-doses of DBP and BPA significantly induced cell apoptosis as they induced ROS generation, blocked cell cycle in G0/G1phase, and inhibited the mRNA transcription of ERα. Therefore, the results will provide experimental data and theoretical direction to comprehensively evaluate the potential health risk of co-exposure of alkyl phenols and phthalic acid esters.
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