Browsing by Subject "MCF-7"

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Chemicals having estrogenic activity can be released from some bisphenol a-free, hard and clear, thermoplastic resins
(BioMed Central, 2014) Bittner, George D.; Denison, Michael S.; Yang, Chun Z.; Stoner, Matthew A.; He, Guochun; Bittner, George D.
Background: Chemicals that have estrogenic activity (EA) can potentially cause adverse health effects in mammals including humans, sometimes at low doses in fetal through juvenile stages with effects detected in adults. Polycarbonate (PC) thermoplastic resins made from bisphenol A (BPA), a chemical that has EA, are now often avoided in products used by babies. Other BPA-free thermoplastic resins, some hypothesized or advertised to be EA-free, are replacing PC resins used to make reusable hard and clear thermoplastic products such as baby bottles. Methods: We used two very sensitive and accurate in vitro assays (MCF-7 and BG1Luc human cell lines) to quantify the EA of chemicals leached into ethanol or water/saline extracts of fourteen unstressed or stressed (autoclaving, microwaving, UV radiation) thermoplastic resins. Estrogen receptor (ER)-dependent agonist responses were confirmed by their inhibition with the ER antagonist ICI 182,780. Results: Our data showed that some (4/14) unstressed and stressed BPA-free thermoplastic resins leached chemicals having significant levels of EA, including one polystyrene (PS), and three Tritan™ resins, the latter reportedly EA-free. Exposure to UV radiation in natural sunlight resulted in an increased release of EA from Tritan™ resins. Triphenyl-phosphate (TPP), an additive used to manufacture some thermoplastic resins such as Tritan™, exhibited EA in both MCF-7 and BG1Luc assays. Ten unstressed or stressed glycol-modified polyethylene terephthalate (PETG), cyclic olefin polymer (COP) or copolymer (COC) thermoplastic resins did not release chemicals with detectable EA under any test condition. Conclusions: This hazard survey study assessed the release of chemicals exhibiting EA as detected by two sensitive, widely used and accepted, human cell line in vitro assays. Four PC replacement resins (Tritan™ and PS) released chemicals having EA. However, ten other PC-replacement resins did not leach chemicals having EA (EA-free-resins). These results indicate that PC-replacement plastic products could be made from EA-free resins (if appropriate EA-free additives are chosen) that maintain advantages of re-usable plastic items (price, weight, shatter resistance) without releasing chemicals having EA that potentially produce adverse health effects on current or future generations.
Estrogenic chemicals often leach from BPA-free plastic products that are replacements for BPA-containing polycarbonate products
(BioMed Central, 2014) Bittner, George D.; Yang, Chun Z.; Stoner, Matthew A.; Bittner, George D.; Yang, Chun Z.; Stoner, Matthew A.
Background: Xenobiotic chemicals with estrogenic activity (EA), such as bisphenol A (BPA), have been reported to have potential adverse health effects in mammals, including humans, especially in fetal and infant stages. Concerns about safety have caused many manufacturers to use alternatives to polycarbonate (PC) resins to make hard and clear, reusable, plastic products that do not leach BPA. However, no study has focused on whether such BPA-free PC-replacement products, chosen for their perceived higher safety, especially for babies, also release other chemicals that have EA. Methods: We used two, well-established, mammalian cell-based, assays (MCF-7 and BG1Luc) to assess the EA of chemicals that leached into over 1000 saline or ethanol extracts of 50 unstressed or stressed (autoclaving, microwaving, and UV radiation) BPA-free PC-replacement products. An EA antagonist, ICI 182,780, was used to confirm that agonist activity in leachates was due to chemicals that activated the mammalian estrogen receptor. Results: Many unstressed and stressed, PC-replacement-products made from acrylic, polystyrene, polyethersulfone, and Tritan™ resins leached chemicals with EA, including products made for use by babies. Exposure to various forms of UV radiation often increased the leaching of chemicals with EA. In contrast, some BPA-free PC-replacement products made from glycol-modified polyethylene terephthalate or cyclic olefin polymer or co-polymer resins did not release chemicals with detectable EA under any conditions tested. Conclusions: This hazard assessment survey showed that many BPA-free PC- replacement products still leached chemicals having significant levels of EA, as did BPA-containing PC counterparts they were meant to replace. That is, BPA-free did not mean EA-free. However, this study also showed that some PC-replacement products did not leach chemicals having significant levels of EA. That is, EA-free PC-replacement products could be made in commercial quantities at prices that compete with PC-replacement products that were not BPA-free. Since plastic products often have advantages (price, weight, shatter-resistance, etc.) compared to other materials such as steel or glass, it is not necessary to forgo those advantages to avoid release into foodstuffs or the environment of chemicals having EA that may have potential adverse effects on our health or the health of future generations.
Variable Response to Chemotherapeutics by a Subpopulation of MCF-7 Breast Cancer Cells
(2016-05-17) Dorland, Julie; Brock, Amy
Several different morphologies can be observed in a population of MCF-7 breast cancer cells, but the typical epithelial morphology vastly predominates. After treatment with the chemotherapeutic doxorubicin, the proportion of abnormal morphologies greatly increases. Over the course of recovery from this drug treatment, the population returns back to high proportions of the normal morphologies. However, previous studies in the Brock lab have shown that in rare instances after recovery from doxorubicin treatment, a phenotype termed the "spiky cells" became stable at higher proportions. This population of spiky cells appeared to have characteristics associated with drug-resistant and metastatic cell populations. In this thesis, I tested the aggressive tumor characteristics of this stable spiky subpopulation and whether it responds differently to doxorubicin. I hypothesized that the growth rate, invasiveness, and drug sensitivity of this population would more closely resemble aggressive tumor cells compared with the naïve MCF-7 population. First, I repeated the induction of the spiky subpopulation with a larger sample size, to determine how frequently this spiky subpopulation occurred. Second, I characterized this subpopulation by comparing four groups: untreated controls of both the normal MCF-7 population and the stable spiky population as well as groups from both populations treated with the same concentration of doxorubicin. I performed these comparisons over the 8-week course of recovery from the treatment. These tests included proliferation rate calculations, invasion assays, staining for a critical protein component of cell-cell junctions, and drug sensitivity tests. We found that the spiky subpopulation appeared more aggressive and resistant, with higher invasion and proliferation, fewer surface markers related to cell connections, and decreased drug sensitivity.