Estrogenicity of bisphenol A and bisphenol A dimethacrylate in vitro

Although pit and fissure sealants have been utilized extensively in dentist ry as a way of preventing occlusal caries, results described by Olea et al. (1996) raised concerns about the safety of sealants and other resin-based dental materials due to the reported presence of bisphenol A (BPA) and its dimethacrylate ester (BPA-DM). Although the release of these compounds from dental materials has not been substantiated by two subsequent studies, we believed it was important to confirm or refute the report that BPA and BPA- DM have estrogenic activity in vitro. We grew breast cancer cells (MCF-7, T -47D, ZR-75-1) known to proliferate under estrogenic stimulation in phenol red-free DMEM containing human serum and concentrations of BPA or BPA-DM ra nging from 10(-8) M to 5 x 10(-6) M. After 1 week, plates were harvested fo r crystal violet or sulforhodamine-B assays, and the optical densities of g roups of treated cells were compared with values from control cells. At con centrations at or above 10(-6) M, both BPA and BPA-DM significantly increas ed cell proliferation (p < 0.05), comparable to the increase seen with 10(- 9) M of estrogen. Flow cytometric methods demonstrated that these mitogenic effects occurred within 24 h of exposure to estrogen, BPA, or BPA-DM. The increase in DNA synthesis was analogous to that seen with estrogen stimulat ion. Thus, we confirmed that BPA and BPA-DM cause cell proliferation at mic romolar concentrations that exceed the effective concentrations of estrogen by 1 to 10,000-fold. (C) 1999 John Wiley & Sons, Inc.