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ToxSci Advance Access published online on May 11, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi188
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Toxicological Sciences © The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received February 21, 2005
Accepted April 21, 2005

Immunotoxiocology

Immunotoxic Effects of Short-term Atrazine Exposure in Young Male C57BL/6 Mice

Nikolay M. Filipov 1* 2, Lesya M. Pinchuk 1 2, Bobbie L. Boyd 1, and Patrick L. Crittenden 1

1 Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, 39762-6100, USA

* To whom correspondence should be addressed.
Nikolay M. Filipov, E-mail: filipov{at}cvm.msstate.edu


  Abstract

The herbicide atrazine (ATR) is a very widely used pesticide; yet the immunotoxicological potential of ATR has not been studied extensively. Our objective was to examine the effect of ATR on selected immune parameters in juvenile mice. ATR (up to 250 mg/kg) was administered by oral gavage for 14 days to 1-month-old male C57BL/6 mice. One day, one week, and 7 weeks after the last ATR dose, mice were sacrificed, and blood, spleens, and thymuses were collected and processed for cell counting and flow cytometry. Thymus and spleen weights were decreased by ATR, with the thymus being more sensitive than the spleen; this effect was still present at 7 days, but not at 7 weeks after the last ATR dose. Similarly, organ cellularity was persistently decreased in the thymus and in the spleen, with the splenic, but not thymic cellularity still being depressed at 7 weeks post ATR. Peripheral blood leukocyte counts were not affected by ATR. There were also alterations in the cell phenotypes in that ATR exposure decreased all phenotypes in the thymus, with the number of CD4+/CD8+ being affected the least. At the higher doses, the decreases in the thymic T cell populations were still present one week after the last ATR dose. In the spleen, the CD8+ were increased and MHC-II+ and CD19+ cells were decreased one day after the last ATR dose. Also, ATR treatment decreased the number of splenic naïve T helper and T cytotoxic cells, whereas it increased the percentage of highly activated cytotoxic/memory T cells. Interestingly, the proportion of mature splenic dendritic cells (DC; CD11chigh), was also decreased and it persisted for at least one week, suggesting that ATR inhibited DC maturation. In the circulation, ATR exposure decreased CD4+ lymphocytes at 1 day, whereas at 7 days after the last ATR dose, in addition to the decrease in CD4+ lymphocytes, the MHC-II+ cells were also decreased at the 250 mg/kg dose. Thus, ATR exposure appears to be detrimental to the immune system of juvenile mice by decreasing cellularity and affecting lymphocyte distribution, with certain effects persisting long after exposure has been terminated.

Keywords: atrazine; pesticide immunotoxicity; C57BL/6 strain; flow cytometry; T cell phenotypes; dendritic cells.

2These two authors contributed equally to this work.


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M. K. Ross, T. L. Jones, and N. M. Filipov
Disposition of the Herbicide 2-Chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine (Atrazine) and Its Major Metabolites in Mice: A Liquid Chromatography/Mass Spectrometry Analysis of Urine, Plasma, and Tissue Levels
Drug Metab. Dispos., April 1, 2009; 37(4): 776 - 786.
[Abstract] [Full Text] [PDF]


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