Di-n-butyl phthalate, butylbenzyl phthalate, and their metabolites exhibit different apoptotic potential in human peripheral blood mononuclear cells

Human peripheral blood mononuclear cells (PBMCs) are one of the main cell models used in studies concerning the exposure of humans (in vitro) to various chemical substances. Changes in PBMCs may reflect the general reaction of the organism regarding the effect of xenobiotics. The aim of this work was to evaluate the effect of di-n-butyl phthalate (DBP), butylbenzyl phthalate (BBP) and their metabolites: mono-n-butylphthalate (MBP), mono-benzylphthalate (MBzP) upon the induction of apoptosis in human peripheral blood mononuclear cells in vitro. PBMCs were incubated with the studied compounds at concentrations from 1 to 100 mu g/mL for 12 h and/or 24 h. In order to clarify the mechanism of phthalates-induced programmed cell death, the changes in the calcium ions (Ca2+) level, alterations in the transmembrane mitochondrial potential (Delta psi m) and caspase-8, -9, -3 activity as well as externalization of phosphatidylserine have been determined. An increased Ca2+ level and a reduction of the Delta psi m were observed in PBMCs incubated with all of the studied compounds, and particularly with DBP and BBP. Phthalates caused an increase of caspases activity. The most pronounced increase was observed for caspase - 9. The most pronounced pro-apoptotic changes were caused by DBP followed by BBP and then by their metabolites.