A Ternary Mixture of Common Chemicals Perturbs Benign Human Breast Epithelial Cells More Than the Same Chemicals Do Individually
| Autor: | Shanaz H. Dairkee, Gloria Luciani-Torres, William H. Goodson, Dan H. Moore, Ian M. Jaffee |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Mitotic index Cell Estrogen receptor Parabens Apoptosis Toxicology Cell Line Xenobiotics Dose-Response Relationship 03 medical and health sciences Breast cancer Phenols Breast Cancer medicine Humans Estrogen Receptor beta Breast Benzhydryl Compounds Carcinogen Cancer Fluorocarbons Dose-Response Relationship Drug Cell growth Chemistry Estrogen Receptor alpha Epithelial Cells Pharmacology and Pharmaceutical Sciences medicine.disease Estrogen 030104 developmental biology medicine.anatomical_structure Cell culture Cancer research Caprylates Drug |
| Zdroj: | Dairkee, SH; Luciani-Torres, G; Moore, DH; Jaffee, IM; & Goodson, WH. (2018). A Ternary Mixture of Common Chemicals Perturbs Benign Human Breast Epithelial Cells More Than the Same Chemicals Do Individually.. Toxicological sciences : an official journal of the Society of Toxicology, 165(1), 131-144. doi: 10.1093/toxsci/kfy126. UC Office of the President: California Breast Cancer Research Program. Retrieved from: http://www.escholarship.org/uc/item/91s7h62w Toxicological sciences : an official journal of the Society of Toxicology, vol 165, iss 1 |
| DOI: | 10.1093/toxsci/kfy126. |
| Popis: | As a continuous source of hormonal stimulation, environmentally ubiquitous estrogenic chemicals, ie, xenoestrogens (XEs), are a potential risk factor for breast carcinogenesis. Given their wide distribution in the environment and the fact that bisphenol-A (BPA), methylparaben (MP), and perfluorooctanoic acid (PFOA) are uniformly detected in unselected body fluid samples, it must be assumed that humans are simultaneously exposed to these chemicals almost daily. We studied the effects of a ternary mixture of BPA, MP, and PFOA on benign breast epithelial cells at the range of concentrations observed for single chemicals in human samples. Measurements of exposure impact relevant to the breast were based on endpoints associated with "hallmarks" of cancer and "key characteristics" of carcinogens. These included modulation of total estrogen receptor (ER)α, phosphorylated ERα (pERα), total ERβ, S-phase induction, and apoptotic evasion. Data from live cell measurements were fit to a log-linear dose-response model. Concentration-dependent reduction of ERβ and apoptosis evasion was observed concurrently with the induction of ERα, pERα, and S-phase fraction, and an increased rate of cell proliferation. Beyond additive effects predicted by the sum of individual test XEs, mixture treatment demonstrated synergism for the ERβ and apoptosis suppression phenotypes (p > .001). Nonmalignant breast cells were more sensitive than commonly used breast cancer lines to XE treatment in 3 of 5 endpoints. All observations were validated with cells isolated from the normal breast tissue of 14 individuals. At relatively low concentrations, a chemical mixture has striking effects on normal cell function that are missed by evaluation of single components. |
| Databáze: | OpenAIRE |
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