- Email: [email protected]
MucilAir: A novel in vitro human 3D airway epithelium model for assessing the potential hazard of nanoparticles and chemical compounds
Abstracts / Toxicology Letters 180S (2008) S32–S246
Z19 MucilAir: A novel in vitro human 3D airway epithelium model for assessing the potential hazard of nanoparticles and chemical compounds Samuel Constant ∗ , Song Huang, Jean-Paul Derouette, Ludovic Wiszniewski Epithelix Sàrl, Geneva, Switzerland Most of the in vitro cell models for long term testing of chemicals suffer of at least two shortcomings: (1) The failure to reproduce the in vivo physiological characteristics of the corresponding tissues, such is the case for the immortalized cell lines. (2) A limited shelflife, as example, the freshly established primary cell cultures. Our company, Epithelix, has developed and is offering a novel in vitro cell model of the human airway epithelium (MucilAir) which is devoid of these limitations. MucilAir is not only morphologically and functionally differentiated; but it can also remain at a homeostatic state for more than one year. Under the electronic microscope, the typical ultra-structures of the human airway epithelium, such as the tight junctions, the cilia, the basal cells, the mucous cells, could be observed. The epithelium is electrically tight with a TEER about 450 cm2 . The ion channels like the sodium channel and chloride channel are fully functional and respond normally to their specific inhibitors and activators when measured in modified Ussing chambers. Moreover, the epithelial cells react to pro-inflammatory mediators such as TNF-␣ in a physiological manner. Remarkably, the epithelium has a strong capacity of regeneration after mechanical or chemical injuries. Due to its fully differentiated feature and a unique shelf-life of one year, this model is a valuable tool for Assessing the potential hazard of nanoparticles and chemical compounds. Epithelix offers ready-to-use products and testing services. doi:10.1016/j.toxlet.2008.06.042 Z20 Hazardous chemicals emergencies in Poland in 2005–2006— Possible public and occupational health impacts Anna Palaszewska-Tkacz, Slawomir Czerczak ∗ Nofer Institute of Occupational Medicine, Lodz, Poland Starting from January 2005, Nofer Institute of Occupational Medicine (NIOM) (Lodz, Poland) collects and analyzes information concerning acute releases of hazardous chemicals. The mentioned project is a direct result of cooperation with Agency for Toxic Substances and Diseases Registry (ATSDR) (Atlanta, USA) which implemented the Hazardous Substances Emergency Events Surveillance (HSEES) system in Poland. The HSEES exists in US from the 1990-ties and it is the effective tool in reducing the harmful effects of dangerous chemicals spills among general public, employees and emergencies responders. The data collected from the beginning of 2005 in Poland illustrate not only the temporal and spatial distribution of emergencies connected with hazardous substances releases but also give a view of morbidity and mortality among employees, first responders and general public. As the identification of the most common risk factors in chemicals emergencies and reduction of the frequency and severity of injuries occurring is one of long-term goals of the study, NIOM developed and described strategies and new rescue action procedures for first responders. We expect them to be more effective during rescue actions. Not only the frequency and detailed structure of hazardous chemicals releases in 2005 and 2006 in Poland, but also rescue
S233
procedures proposed for each separate substance or group of substances are to be presented. doi:10.1016/j.toxlet.2008.06.043 Z21 The literature-extracted database functions—A novel drug discovery tool
of
small
molecule
Nikolai Daraselia Ariadne Genomics, Rockville, MD, United States Efficient drug research and development process requires an indepth understanding of the molecular, cellular and toxicological properties and mechanisms of a drug candidate. Relevant pieces of information are scattered as free text among thousands of scientific publications and reports, and bringing them together is a serious challenge. The latest advances in automated information extraction techniques offer a unique opportunity to bridge the gap between free-text and structured knowledge in the drug development field. We have developed a unique technology for automatic extraction of biological and pharmacological information about small molecules, including: Small molecule-protein binding; protein targets and direct inhibition/activation of a protein by drugs; protein expression changes in response to drug treatments; pharmacological drug effects, including effects on cellular and physiological processes and diseases; drug metabolism and transport; protein biomarkers of toxicities. We have applied this technology to entire Pubmed and 60 freely available full-text journals to extract more that 500,000 unique relationships describing functions of 22,000 small molecules, 8800 proteins, 1963 cellular processes, and 4600 physiological processes and diseases. This information is available via a knowledge management system, Pathway Studio, which provides data search and analysis, literature mining and pathway building capabilities. This unique and highly integrated cross-domain knowledge resource provides access to the latest information about all aspects of drug mechanisms, metabolism, and toxicity; all information is linked to the corresponding literature sources. The knowledgebase also provides structural information for more than 277,000 small molecules by linking them to PubChem. doi:10.1016/j.toxlet.2008.06.044 Z22 Transport of MCPA (4-chloro-2-methylphenoxyacetic acid) across Caco-2 Cell monolayer by monocarboxylic acid transporters Osamu Kimura ∗ , Kensuke Tukagoshi, Tetsuya Endo Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan The purpose of this study using epithelial cells, Caco-2, cultured on the permeable membranes was to confirm the cellular uptake of 4chloro-2-methylphenoxyacetic acid (MCPA), a phenoxyacetic acid derivative, by monocarboxylic acid transporters (MCTs) (Kimura et al., 2008). The cells were incubated with 50 M MCPA from the apical side or basolateral side, and the cellular uptake and the transcellular transport of MCPA were measured. The initial uptake of MCPA from the apical side (pH 7.4) and the transport of MCPA from apical side to basolateral side (pH 7.4) were similar to those of the uptake and transport of MCPA from the basolateral to apical side, respectively. The decrease in pH of apical side from pH
Z19 MucilAir: A novel in vitro human 3D airway epithelium model for assessing the potential hazard of nanoparticles and chemical compounds Samuel Constant ∗ , Song Huang, Jean-Paul Derouette, Ludovic Wiszniewski Epithelix Sàrl, Geneva, Switzerland Most of the in vitro cell models for long term testing of chemicals suffer of at least two shortcomings: (1) The failure to reproduce the in vivo physiological characteristics of the corresponding tissues, such is the case for the immortalized cell lines. (2) A limited shelflife, as example, the freshly established primary cell cultures. Our company, Epithelix, has developed and is offering a novel in vitro cell model of the human airway epithelium (MucilAir) which is devoid of these limitations. MucilAir is not only morphologically and functionally differentiated; but it can also remain at a homeostatic state for more than one year. Under the electronic microscope, the typical ultra-structures of the human airway epithelium, such as the tight junctions, the cilia, the basal cells, the mucous cells, could be observed. The epithelium is electrically tight with a TEER about 450 cm2 . The ion channels like the sodium channel and chloride channel are fully functional and respond normally to their specific inhibitors and activators when measured in modified Ussing chambers. Moreover, the epithelial cells react to pro-inflammatory mediators such as TNF-␣ in a physiological manner. Remarkably, the epithelium has a strong capacity of regeneration after mechanical or chemical injuries. Due to its fully differentiated feature and a unique shelf-life of one year, this model is a valuable tool for Assessing the potential hazard of nanoparticles and chemical compounds. Epithelix offers ready-to-use products and testing services. doi:10.1016/j.toxlet.2008.06.042 Z20 Hazardous chemicals emergencies in Poland in 2005–2006— Possible public and occupational health impacts Anna Palaszewska-Tkacz, Slawomir Czerczak ∗ Nofer Institute of Occupational Medicine, Lodz, Poland Starting from January 2005, Nofer Institute of Occupational Medicine (NIOM) (Lodz, Poland) collects and analyzes information concerning acute releases of hazardous chemicals. The mentioned project is a direct result of cooperation with Agency for Toxic Substances and Diseases Registry (ATSDR) (Atlanta, USA) which implemented the Hazardous Substances Emergency Events Surveillance (HSEES) system in Poland. The HSEES exists in US from the 1990-ties and it is the effective tool in reducing the harmful effects of dangerous chemicals spills among general public, employees and emergencies responders. The data collected from the beginning of 2005 in Poland illustrate not only the temporal and spatial distribution of emergencies connected with hazardous substances releases but also give a view of morbidity and mortality among employees, first responders and general public. As the identification of the most common risk factors in chemicals emergencies and reduction of the frequency and severity of injuries occurring is one of long-term goals of the study, NIOM developed and described strategies and new rescue action procedures for first responders. We expect them to be more effective during rescue actions. Not only the frequency and detailed structure of hazardous chemicals releases in 2005 and 2006 in Poland, but also rescue
S233
procedures proposed for each separate substance or group of substances are to be presented. doi:10.1016/j.toxlet.2008.06.043 Z21 The literature-extracted database functions—A novel drug discovery tool
of
small
molecule
Nikolai Daraselia Ariadne Genomics, Rockville, MD, United States Efficient drug research and development process requires an indepth understanding of the molecular, cellular and toxicological properties and mechanisms of a drug candidate. Relevant pieces of information are scattered as free text among thousands of scientific publications and reports, and bringing them together is a serious challenge. The latest advances in automated information extraction techniques offer a unique opportunity to bridge the gap between free-text and structured knowledge in the drug development field. We have developed a unique technology for automatic extraction of biological and pharmacological information about small molecules, including: Small molecule-protein binding; protein targets and direct inhibition/activation of a protein by drugs; protein expression changes in response to drug treatments; pharmacological drug effects, including effects on cellular and physiological processes and diseases; drug metabolism and transport; protein biomarkers of toxicities. We have applied this technology to entire Pubmed and 60 freely available full-text journals to extract more that 500,000 unique relationships describing functions of 22,000 small molecules, 8800 proteins, 1963 cellular processes, and 4600 physiological processes and diseases. This information is available via a knowledge management system, Pathway Studio, which provides data search and analysis, literature mining and pathway building capabilities. This unique and highly integrated cross-domain knowledge resource provides access to the latest information about all aspects of drug mechanisms, metabolism, and toxicity; all information is linked to the corresponding literature sources. The knowledgebase also provides structural information for more than 277,000 small molecules by linking them to PubChem. doi:10.1016/j.toxlet.2008.06.044 Z22 Transport of MCPA (4-chloro-2-methylphenoxyacetic acid) across Caco-2 Cell monolayer by monocarboxylic acid transporters Osamu Kimura ∗ , Kensuke Tukagoshi, Tetsuya Endo Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan The purpose of this study using epithelial cells, Caco-2, cultured on the permeable membranes was to confirm the cellular uptake of 4chloro-2-methylphenoxyacetic acid (MCPA), a phenoxyacetic acid derivative, by monocarboxylic acid transporters (MCTs) (Kimura et al., 2008). The cells were incubated with 50 M MCPA from the apical side or basolateral side, and the cellular uptake and the transcellular transport of MCPA were measured. The initial uptake of MCPA from the apical side (pH 7.4) and the transport of MCPA from apical side to basolateral side (pH 7.4) were similar to those of the uptake and transport of MCPA from the basolateral to apical side, respectively. The decrease in pH of apical side from pH