Alterations of A549 lung cell gene expression in response to biochemical toxins |
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Authors: | D E Boesewetter J L Collier A M Kim M R Riley |
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Institution: | (1) Department of Agricultural and Biosystems Engineering, The University of Arizona, Tucson, Arizona, USA;(2) Department of Agricultural and Biosystems Engineering, University of Arizona, Tucson, A2857, USA |
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Abstract: | Health risks associated with the inhalation of potentially toxic materials have been a topic of great public concern. In vitro cellular analyses can provide mechanistic information on the molecular-level responses of lung-derived cell lines to a variety
of these hazards. This understanding may be used to develop methods to reduce the damage from such toxins or to detect early
stages of their effects. Here we describe an evaluation of the alterations in gene expression of an immortalized lung cell
line (A549, human type II epithelia) to a variety of inhalation health hazards including etoposide, gliotoxin, streptolysin
O, methyl methansesulfonate (MMS), and Triton X-100. The A549 cells display a dose–response relationship to each toxin with
initial responses including alterations in metabolic activity, increases in membrane permeability, and initiation of response
genes. In general, membrane-damaging agents (streptolysin O and Triton X-100) induce production of new ion channel proteins,
structural proteins, and metabolic enzymes. Gliotoxin impacted the metabolic machinery, but also altered ion channels. Etoposide
and MMS caused alterations in the cell cycle, induced DNA repair enzymes, and initiated apoptotic pathways, but MMS also induced
immune response cascades. The mechanism of cell response to each toxin is supported by physiological analyses that indicated
a fairly slow initiation of cell response to all compounds tested, except for Triton, which caused rapid decline in cell function
due to solubilization of the cell membrane. However, Triton does induce production of a number of cell membrane-associated
proteins and so its effects at low concentrations are likely translated throughout the cell. Together these results indicate
a broader array of cellular responses to each of the test toxins than have previously been reported. |
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Keywords: | cell culture gene expression human lung cells inhalation hazards |
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