Comparative in vitro cytotoxicity assessment of selected gaseous compounds in human alveolar epithelial cells. 2007

S Bakand, and C Winder, and A Hayes
Chemical Safety and Applied Toxicology (CSAT) Laboratories, School of Safety Science, The University of New South Wales, UNSW Sydney 2052, Australia.

Exposure to airborne contaminants is significantly associated with human health risks, ranging from bronchial reactivity to morbidity and mortality due to acute intense or long term low level repeated exposures. However, the precise mechanisms that derive such effects are not always understood. Although inhalation studies are technologically complicated, correct hazard characterisation is essential for comparable risk assessment of inhaled materials. The aim of this study was to investigate the comparative in vitro cytotoxicity of selected gaseous contaminants in human lung cells. The cytotoxicity of nitrogen dioxide (NO(2)), sulphur dioxide (SO(2)) and ammonia (NH(3)) was investigated in A549- human pulmonary type II-like epithelial cell lines cultured on porous membranes in Snapwell inserts. A dynamic direct exposure method was established by utilizing the horizontal diffusion chamber system (Harvard Apparatus Inc, USA) for delivery of test atmospheres. Test atmospheres were generated using a dynamic direct dilution method and the concentration monitored by appropriate analytical methods. A diversified battery of in vitro assays including the MTS (tetrazolium salt; Promega), NRU (neutral red uptake; Sigma) and ATP (adenosine triphosphate; Promega) assays was implemented. Airborne IC(50) (50% inhibitory concentration) values were calculated based on the most sensitive assay for each test gas including NO(2) (IC(50)=11+/-3.54 ppm; NRU)>SO(2) (IC(50)=48+/-2.83 ppm; ATP)> and NH(3) (IC(50)=199+/-1.41 ppm; MTS). However, all in vitro assays revealed similar toxicity ranking for selected gaseous contaminants. Identical toxicity ranking was achieved using both in vitro and published in vivo data. This comparison suggests that results of in vitro methods are comparable to in vivo data and may provide greater sensitivity for respiratory toxicity studies of gaseous contaminants.

UI MeSH Term Description Entries
D009585 Nitrogen Dioxide Nitrogen oxide (NO2). A highly poisonous gas. Exposure produces inflammation of lungs that may only cause slight pain or pass unnoticed, but resulting edema several days later may cause death. (From Merck, 11th ed) It is a major atmospheric pollutant that is able to absorb UV light that does not reach the earth's surface. Nitrogen Peroxide,Dioxide, Nitrogen,Peroxide, Nitrogen
D011650 Pulmonary Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Alveoli, Pulmonary,Alveolus, Pulmonary,Pulmonary Alveolus
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004847 Epithelial Cells Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells. Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell
D005740 Gases The vapor state of matter; nonelastic fluids in which the molecules are in free movement and their mean positions far apart. Gases tend to expand indefinitely, to diffuse and mix readily with other gases, to have definite relations of volume, temperature, and pressure, and to condense or liquefy at low temperatures or under sufficient pressure. (Grant & Hackh's Chemical Dictionary, 5th ed)
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000393 Air Pollutants Any substance in the air which could, if present in high enough concentration, harm humans, animals, vegetation or materials. Substances include GASES; PARTICULATE MATTER; and volatile ORGANIC CHEMICALS. Air Pollutant,Air Pollutants, Environmental,Environmental Air Pollutants,Environmental Pollutants, Air,Air Environmental Pollutants,Pollutant, Air,Pollutants, Air,Pollutants, Air Environmental,Pollutants, Environmental Air
D000641 Ammonia A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as AMMONIUM HYDROXIDE.
D013458 Sulfur Dioxide A highly toxic, colorless, nonflammable gas. It is used as a pharmaceutical aid and antioxidant. It is also an environmental air pollutant. Sulfurous Anhydride
D018675 Toxicity Tests An array of tests used to determine the toxicity of a substance to living systems. These include tests on clinical drugs, foods, and environmental pollutants. Tests, Toxicity,Test, Toxicity,Toxicity Test

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