The endocrine disruptor Bisphenol A affects cell proliferating ability in PHA-stimulated peripheral lymphocytes exerting a biphasic effect

Abstract

In the last two decades, a growing number of studies highlighted the importance of the interaction between the estrogen-receptor pathway modulation and immune cell activity in human metabolic regulation [1]. It is recognized that steroid pathways can regulate immune cell metabolism and thus the intacrine-paracrine effects of steroids could be implicated in pro- moting immune-mediated steroid-dependent cancers and autoimmune diseases. Moreover, it has been shown that both monocytes and T-lymphocytes express estrogen receptors (ERα and ERβ) [2], therefore it is plausible that environmental pollutants interfering with steroid path- ways, such as Bisphenol A (BPA) -a widespread contaminant of plastic, epoxy resins, toys and electronics with structural and functional similarities to steroids - could influence immune cell activity leading to cancer, autoimmune disease and neurological disorders. To gain insights into this issue, we studied the effects of BPA in Phytoemagglutinin (PHA)-stimulated Peripheral Blood Mononuclear Cells (PBMCs) from healthy donors examining cell survival by MTT assay, cell proliferation by BrdU assay, and cell cycle progression by cytofluorimetric analysis at differ- ent time points (24-72 hs) and concentrations (ranging from 5 nM to 200 μM).

Results show that BPA does not induce apoptosis or necrosis, at all time and doses tested, instead promotes cell proliferation at lowest concentrations. Cytofluorimetric analysis by Pro- pidium Iodide staining also indicates that BPA is able to emphasize PHA-induced effects in enhancing cell proliferation at concentrations ranging from 25 to 100 nM. However, the com- pound markedly inhibits cell cycle progression at concentrations greater than 25 μM causing a G1 cell cycle arrest starting from 24 hs of treatment. On the other hand, BPA was unable to induce any effect in resting PBMCs, suggesting that BPA -induced biphasic effect in proliferat- ing cells could be the result of mechanisms other than its estrogen-like behavior.