Mitochondrial permeability and toxicity of diethylhexyl and monoethylhexyl phthalates on TK6 human lymphoblasts cells
| Autor: | Beatriz Zayas, Christian Velez, Carlos A. Rosado-Berrios |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Programmed cell death
T-Lymphocytes Phthalic Acids Caspase 3 Apoptosis Mitochondrion Toxicology Permeability Article chemistry.chemical_compound Cell Line Tumor Humans Viability assay Inner mitochondrial membrane Caspase Caspase 7 Membrane Potential Mitochondrial biology Phthalate General Medicine Cell biology Mitochondria chemistry Biochemistry biology.protein Environmental Pollutants Reactive Oxygen Species |
| Zdroj: | Toxicology in vitro : an international journal published in association with BIBRA. 25(8) |
| ISSN: | 1879-3177 |
| Popis: | Phthalates are ubiquitous compounds used in the manufacturing industry. Some are known endocrine disruptors, acting as xenoestrogens, others induce reproductive toxicity and damage to DNA among other effects. Studies on apoptosis induction and mitochondrial damage capacity of phthalates on the immune system are limited. This study aims to determine cell viability inhibition and apoptosis induction of diethylhexyl phthalate (DEHP) and monoethylhexyl phthalate (MEHP) on the human TK6 lymphoblast cell line at concentrations found in the environment. Key hallmark events, such as mitochondrial membrane permeability, generation of reactive oxygen species (ROS) and activation of caspase 3 and 7 were measured. Concentrations that inhibit viability of 50% (IC50) of the cells were determined at 24, 48 and 72 hours with doses ranging from 10μM to 500μM. Changes in mitochondrial membrane permeability, ROS generation and activation of caspases 3 and 7, were measured as part of the cell death mechanism. The IC50 at 24 hours was approximately 250 μM for both phthalates; at 48 hours were 234μM and 196μM for DEHP and MEHP, respectively and at 72 hours IC50s were 100 μM and 80 μM for DEHP and MEHP respectively. Overall the longer the time of exposure the lower the IC50's for both compounds. Both compounds affected mitochondrial membrane potential, promoted ROS generation and activated caspases 3 and 7. MEHP is more toxic, promotes higher level of ROS production and caspases activation. Our findings suggest that DEHP and MEHP have the capacity to induce apoptosis in cells of the immune system at concentrations found in the environment. |
| Databáze: | OpenAIRE |
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