BioProject

The prostate is one of the main accessory glands of the male reproductive system, responsible of up to 30% of the secretions constituting seminal plasma, and is essential for male fertility (Burden et al. More...

The prostate is one of the main accessory glands of the male reproductive system, responsible of up to 30% of the secretions constituting seminal plasma, and is essential for male fertility (Burden et al. 2006 and references therein). Animal studies have shown that phthalates can trigger cellular events associated with the onset of prostatic diseases. There is increasing interest in developing safe alternative plasticizers to phthalates. Many potential candidates were recently reported, and their mechanisms of action on prostatic cells warrant investigation. The goal of this study was to evaluate the toxicity of four families of chemicals that are candidate plasticizer using a non-cancerous human prostate cell line, PNT1A. These candidate plasticizers were compared to diethylhexyl phthalate (DEHP), its main bioactive metabolite monohexylethyl phthalate (MEHP), and a current “green” plasticizer that is being used increasingly, 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), using a combination of classical (MTT) and high throughput techniques (HCS, microarray). High content screening provided additional information about cell counts and range of parameters related to cell function. The incorporation of gene expression studies revealed that several of the compounds tested in this study had an effect on cellular functions, even those that had not shown any effect with the other assays. While DINCH was found to have wide ranging effects, we show that candidate plasticizers of the dibenzoate family have no effects on metabolic activity, cellular morphology, cellular proliferation or gene expression in PNT1A cells. Candidate plasticizers of the succinate family had an effect only at the gene expression level. Overall design: Ten treatments are compared to the 0.4% DMSO control: Five compounds (DHS, DINCH, DOM, DOS, MEHP) at two different concentrations (mid = 10E-6M, low = 10E-8M). MEHP_low was analyzed in triplicate, whereas the other treatments were analyzed in quadriplicate Less...