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ToxSci Advance Access originally published online on July 25, 2003
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Toxicological Sciences 75, 343-354 (2003)
Copyright © 2003 by the Society of Toxicology


IMMUNOTOXICOLOGY

Modeling and Predicting Immunological Effects of Chemical Stressors: Characterization of a Quantitative Biomarker for Immunological Changes Caused by Atrazine and Ethanol

Stephen B. Pruett1, Ruping Fan, Qiang Zheng, L. Peyton Myers and Pamela Hébert

Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130

Previous studies demonstrate that the effects of one chemical stressor on selected immunological parameters can be predicted on the basis of the area under the corticosterone concentration vs. time curve. However, it is not clear if this is applicable to other chemical stressors. The present study was conducted to determine if the stress-induced immunological effects of atrazine and ethanol could be predicted, and if it is feasible to use one immunological parameter as a biomarker of stress to predict the quantity of changes expected in other immunological parameters. The area under the corticosterone concentration-versus-time curve (AUC) was measured in mice treated with ethanol (EtOH, 4, 5, 6, or 7 g/kg by oral gavage) or atrazine (ATZ, 100, 200, or 300 mg/kg, ip). The effects of the same dosages of these chemicals on thymus and spleen cellularity, lymphocyte subpopulations in the thymus and spleen, expression of MHC class II protein on splenocytes, antibody responses to keyhole limpet hemocyanin, and natural killer-cell activity were determined. Models were derived describing the relationship between corticosterone AUC and immunological changes induced by these chemicals. The results for these chemical stressors were more similar to results obtained from mice subjected to restraint stress than from mice treated with exogenous corticosterone. Some effects were greater than predicted on the basis of the stress response alone, indicating other mechanisms of immunotoxicity. One of the parameters (MHC class II expression) was evaluated as a predictive biomarker for stress-related immunosuppression, and the results suggest it could be suitable for that purpose.

Key Words: stress; corticosterone; atrazine; ethanol; predictive model; biomarker.


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