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ToxSci Advance Access originally published online on November 2, 2007
Toxicological Sciences 2008 101(2):263-274; doi:10.1093/toxsci/kfm274
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© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

In Vitro Exposure of Jurkat T-Cells to Industrially Important Organic Solvents in Binary Combination: Interaction Analysis

Catherine McDermott*,{dagger}, Ashley Allshire*,{ddagger}, Frank van Pelt*,{ddagger} and James J. A. Heffron*,§,1

* Environmental Research Institute {dagger} Department of Biochemistry {ddagger} Department of Pharmacology and Therapeutics § Department of Biochemistry, University College Cork, Lee Maltings, Cork 1, Ireland

1 To whom correspondence should be addressed at Department of Biochemistry, University College Cork, Lee Maltings, Prospect Row, Cork, Ireland. Fax: +35-32-14-90-42-15. E-mail: j.heffron{at}ucc.ie.

Received August 15, 2007; accepted October 30, 2007


  Abstract

Humans are frequently exposed to mixtures of environmental pollutants at low levels over prolonged periods of time yet most toxicity studies deal with acute exposure to high concentrations of single chemicals. Investigation of the biological effects and possible toxic interactions during long-term exposure to such mixtures is warranted. Here Jurkat T-cells were exposed to toluene, n-hexane and methyl ethyl ketone in binary combination. Concentration ranges were centered on thresholds at which the individual agents caused cell toxicity under otherwise similar conditions, and concentrations were confirmed by headspace gas chromatography. After 5 days cells were harvested and toxicity measured in terms of membrane damage (lactate dehydrogenase [LDH] leakage), perturbations in [Ca2+]i and changes in glutathione redox status. Data for all three endpoints were subjected to isobolographic analysis to test for interaction between components of the solvent mixture. Almost all combinations of toluene and n-hexane elicited greater than additive toxicity in terms of each of the three endpoints, as did methyl ethyl ketone (MEK)/n-hexane and MEK/toluene combinations for the LDH and glutathione endpoints. The main exceptions were the two combinations involving MEK, which caused less than additive effects on perturbations of [Ca2+]i. It is concluded that toxicity in immune-derived T cells may exhibit greater than additive effects when there is coexposure to organic solvents. This may have implications for risk assessment of environmental exposure to these agents.

Key Words: mixture toxicity; in vitro; organic solvent; isobolographic analysis.


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