Abstract
Exposure to the endocrine disruptor bisphenol A (BPA) has been linked with immune disorders and increased tumour risk. Our previous work in activated human peripheral blood mononuclear cells demonstrated that exposure to "low-dose" BPA diminished telomerase activity via an ER/GPR30-ERK signalling pathway. Leukocyte telomerase activity and telomere maintenance are crucial for normal immune function and homeostasis. We thus here further studied the effects of BPA on human T cell subpopulations. Exposure to 0.3-3 nM BPA, i. e. at doses in the realm of human exposure, notably reduced telomerase activity in activated CD8 + T but not CD4 + T cells in a non-monotonic response pattern as determined by the TRAP-ELISA assay. Under long-term BPA exposure, significant telomere length shortening, reduction in mitochondrial DNA copy number, cell proliferation and IFN-γ as well as hTERT protein suppression could be observed in CD8 + lymphocytes, as analysed by qRT-PCR, flow cytometry and western blot analysis. This study extends our previous in vitro findings that "low-dose" BPA has potential negative effects on healthy human cytotoxic T cell response. These results might merit some special attention to further investigate chronic BPA exposure in the context of adaptive immune response dysfunction and early onset of cancer in man.