Exposure to cyclic volatile methylsiloxanes (cVMS) causes anchorage-independent growth and reduction of BRCA1 in non-transformed human breast epithelial cells

摘要

Dermal absorption of components of personal care products (PCPs) may contribute to breast cancer development. Cyclic volatile methylsiloxanes (cVMS) are used widely in the formulation of PCPs, and their presence has been recently detected in human blood. The objectives of this study were to investigate any genotoxic effects after short- (1week) or longer-term (30weeks) exposure to hexamethylcyclotrisiloxane (D3), octamethylcyclotetrasiloxane (D4) or decamethylcyclopentasiloxane (D5) in MCF-10A and MCF-10F immortalized non-transformed human breast epithelial cells. Genotoxic effects were assessed by an ability of cells to grow in suspension culture, from DNA damage measured by comet assays, and from a reduction in levels of DNA repair proteins measured by RT-PCR and western immunoblotting. Dose-dependent anchorage-independent growth in methocel culture was observed after exposure to D3 (10(-13)M-10(-5)M) and D4/D5 (10(-9)M-10(-5)M). DNA damage was measured by the comet assay after 1-h exposure to D3 (10(-6)M-10(-5)M) and D4 (10(-5)M). BRCA1 mRNA and BRCA1 protein levels were reduced after 30-week exposure to 10(-5)M D4 and D5 in both cell lines. Reduced levels of mRNAs for other DNA repair proteins (BRCA2, ATM, ATR, CHK1 and CHK2) were also observed after exposure to 10(-5)M D5 in both cell lines, and some reductions after exposure to D3 and D4. If cVMS can not only enable anchorage-independent growth of non-transformed breast epithelial cells and damage DNA, but also compromise DNA repair systems, then there is the potential for them to impact on breast carcinogenesis. Further risk assessment now requires information concerning the extent to which cVMS may be present in human breast tissues. Copyright (c) 2016 John Wiley & Sons, Ltd.