Publicação
Low-dose effects of Bisphenol A on human primary vascular endothelial cells and colon cancer cells
| Resumo: | Bisphenol A (BPA) is an extensively utilized endocrine disruptor for which human exposure is considered generalized through ingestion. Information regarding BPA effects on vascular and digestive tract tissues is scarce. Therefore, in this work primary Human Umbilical Vein Endothelial Cells (HUVEC) and human colon adenocarcinona cell line HT29 were used to evaluate BPA effects at two distinct low-dose concentrations relevant in terms of human health risk assessment. BPA differentially affects the cell types studied, with more pronounced aneugenic effects, nucleolar disruption and transcriptional deregulation observed in HUVEC. Prolonged BPA exposure affects aging processes in senescent HUVEC. Interaction experiments involving expression of key cancer related genes shows that BPA antagonizes transcriptional effects of the chemotherapeutic agent doxorubicin in HT29. Additionally BPA aneugenic effects are enhanced by co-exposure with Eupatorium cannabinum L. ethanolic extract, a medicinal plant, for which a potent cytotoxic activity against HT29 cells is also demonstrated here. Altogether these results support increasing concerns regarding harmful effects of BPA at low-dose on human health and draw attention to the importance of a deeper understanding of BPA potential interactions with other chemicals. |
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| Autores principais: | Varandas, Edna Soraia Gregório Ribeiro |
| Assunto: | Bisphenol A (BPA) HUVEC HT29 gene transcription drug interaction |
| Ano: | 2014 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Bisphenol A (BPA) is an extensively utilized endocrine disruptor for which human exposure is considered generalized through ingestion. Information regarding BPA effects on vascular and digestive tract tissues is scarce. Therefore, in this work primary Human Umbilical Vein Endothelial Cells (HUVEC) and human colon adenocarcinona cell line HT29 were used to evaluate BPA effects at two distinct low-dose concentrations relevant in terms of human health risk assessment. BPA differentially affects the cell types studied, with more pronounced aneugenic effects, nucleolar disruption and transcriptional deregulation observed in HUVEC. Prolonged BPA exposure affects aging processes in senescent HUVEC. Interaction experiments involving expression of key cancer related genes shows that BPA antagonizes transcriptional effects of the chemotherapeutic agent doxorubicin in HT29. Additionally BPA aneugenic effects are enhanced by co-exposure with Eupatorium cannabinum L. ethanolic extract, a medicinal plant, for which a potent cytotoxic activity against HT29 cells is also demonstrated here. Altogether these results support increasing concerns regarding harmful effects of BPA at low-dose on human health and draw attention to the importance of a deeper understanding of BPA potential interactions with other chemicals. |
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