Abstract
Perfluorooctanesulfonic acid (PFOS) is a synthetic fluorosurfactant widely used in the industry and a prominent environmental toxicant. PFOS is persistent, bioaccumulative, and toxic to mammalian species. Growing evidence suggests that PFOS has the potential to interfere with estrogen homeostasis, posing a risk of endocrine-disrupting effects. Recently, concerns about a potential link between PFOS and breast cancer have been raised, but the mechanisms underlying its actions as a potential carcinogen are unknown. By utilizing cell proliferation assays, flow cytometry, immunocytochemistry, and cell migration/invasion assays, we examined the potentially tumorigenic activity of PFOS (100 nM–1 mM) in MCF-10A breast cell line. The results showed that the growth of MCF-10A cells exposed to 1 and 10 µM PFOS was higher compared to that of the control. Mechanistic studies using 10 µM PFOS demonstrated that the compound promotes MCF-10A proliferation through accelerating G0/G1-to-S phase transition of the cell cycle after 24, 48, and 72 h of treatment. In addition, PFOS exposure increased CDK4 and decreased p27, p21, and p53 levels in the cells. Importantly, treatment with 10 µM PFOS for 72 h also stimulated MCF-10A cell migration and invasion, illustrating its capability to induce neoplastic transformation of human breast epithelial cells. Our experimental results suggest that exposure to low levels of PFOS might be a potential risk factor in human breast cancer initiation and development.
Highlights
Perfluorooctanesulfonic acid (PFOS), is a man-made fluorosurfactant that has been used as lubricant, component of polishes, paints, paper, textile coatings, food packaging, and fire-retardant foams (Lindstrom et al 2011)
We investigated the effects of PFOS exposure in the human normal breast epithelial cell line, MCF10A, at various concentrations (100 nM–1 mM) and different time points (24, 48 and 72 h)
To determine whether PFOS exposure can induce cell death or proliferation, cells were incubated with 0–1 mM PFOS for 24, 48, and 72 h, and cell viability determined by the MTT assay
Summary
Perfluorooctanesulfonic acid (PFOS), is a man-made fluorosurfactant that has been used as lubricant, component of polishes, paints, paper, textile coatings, food packaging, and fire-retardant foams (Lindstrom et al 2011). Due to its water solubility and resistance to biological degradation, PFOS is mobilized and released from landfills in water bodies, and bio-accumulates in food chains (Giesy et al 2001; Parsons et al 2008). Humans are exposed to PFOS via oral, inhalation, and dermal routes. For the general population, ingestion of fish and drinking water are the main sources of PFOS exposure. PFOS are detected in concentrations of up to 48 ng/ml in human samples such as serum and breast milk, depending on the country and dietary intake (Karrman et al 2007; Sundstrom et al 2011). PFOS exposure can result in a variety of toxic effects, including liver toxicity, developmental toxicity, and immunotoxicity (Chang et al 2008; Saikat et al 2013). PFOS is suspected to be an endocrine disruptor with estrogenic activity (Jensen and Leffers 2008), and may contribute to the risk of breast cancer (Bonefeld-Jorgensen et al 2011), but the potential for PFOS to contribute to endocrine disruption in mammalians is not well defined
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