Browsing by Subject "Environmental Health Sciences"
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Item Effects of TCDD on MCF10A cells in 2D and 3D Cultures(2012-04-18) Drachenberg, Disa2,3,7,8 –tetrachlorodibenzo-p-dioxin (known as dioxin or TCDD) is a chemical pollutant that can be found in drinking water, soil, dust, and air. TCDD has a biological half-life of 7-10 years in humans. It is unethical to study the effects of TCDD on humans and the use of an animal model may not always relevant to humans. A reasonable alternative is to use 3-dimensional human cell culture. The human breast epithelial cell line MCF10A represents normal breast tissue and can be grown in 3D culture. In contrast to traditional 2D culture, MCF10A cells form secondary structures, called acini, when grown in 3D culture. Studying acini offers a unique advantage because these structures more accurately portray tissue growth and development in vivo. TCDD binds to the aryl hydrocarbon receptor (AhR) and can induce cytochrome P450s and growth factors. In these experiments MCF10A cells were grown in 2D or 3D culture and were exposed to TCDD or left untreated. AhR mediated gene expression of two cytochrome P450s, CYP1A1 and CYP1B1, were measured.Item Investigation of furan metabolite BDApolyamine crosslinks in cell toxicity and carcinogenesis(2012-04-18) Bonglack, MildredeFuran is a product of incomplete combustion present in canned foods, tobacco smoke and exhaust fumes. It has been shown to be a liver toxicant and carcinogen in rodents. This project seeks to determine the toxic carcinogenic effect of furan in human liver cells as these remains unknown. Cis-2-butene-1,4-dial (BDA), a highly reactive breakdown product of furan, has been shown to form stable crosslinks with polyamines and glutathione in vivo and in cell models. The spermine and ornithine crosslinks were synthesized and purified using high pressure liquid chromatography and characterized using mass spectrometry and nuclear magnetic resonance. The synthesized crosslinks will be introduced into human liver cell cultures to study if these products of furan metabolism play a role in liver toxicity and carcinogenicity. These data will be combined with others to determine if furan is a human health concern.