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Characterization of thymic atrophy and the mechanism of thymocyte depletion after in vivo exposure to a mixture of herbicides.
J Toxicol Environ Health A. 2005 Jan 22; 68(2):81-98.JT

Abstract

3,4-Dichloropropionanilide (propanil) and 2,4-dichlorophenoxyacetic acid (2,4-D) are two commonly used herbicides that are marketed as a chemical mixture. It was hypothesized that the interaction between these two herbicides, when administered as a mixture, would result in a greater effect on the immune system than the individual components of the mixture. The present study demonstrates in a murine model that a mixture of propanil and 2,4-D, when compared to single herbicide exposures, exacerbates decreases in thymocyte populations 2 d postexposure and inhibits the repopulation of T-cells in the thymus 7 d postexposure. Exposure to 150 mg herbicide/kg body weight of propanil or 2,4-D alone had no effect on thymus weight. In contrast, decreases in the ratio of thymus weight to body weight (TW:BW) occurred 2 d after treatment with the mixture of 150 mg propanil/kg body weight + 150 mg 2,4-D/kg body weight (150/150). Thymic atrophy was associated with a decrease in the double-positive thymocyte population (CD4+CD8+) and correlated with sera corticosterone levels from 600 to 1000 pg/ml. Therefore, the hypothesis was tested that glucocorticoids, induced after exposure to herbicides, were responsible for the thymic atrophy and depletion of thymocytes. However, similar levels of corticosterone were induced after exposure to 50, 100, or 150 mg propanil/kg body weight, and 50/50 or 100/100 mixture treatments, doses that did not produce thymic atrophy or cell loss. In addition, RU 486, a glucocorticoid receptor blocker, only partially abrogated the thymic atrophy in mice exposed to the 150/150 mixture of herbicides. These results suggest that glucocorticoids are only partially responsible for herbicide-induced thymic atrophy. This study demonstrates that the effects of exposure to a mixture of chemicals cannot always be predicted based on single exposure data and emphasizes the importance of mixture-based studies.

Authors+Show Affiliations

NIOSH-HELD-ASB, Morgantown, West Virginia, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15762548

Citation

de la Rosa, Patricia, et al. "Characterization of Thymic Atrophy and the Mechanism of Thymocyte Depletion After in Vivo Exposure to a Mixture of Herbicides." Journal of Toxicology and Environmental Health. Part A, vol. 68, no. 2, 2005, pp. 81-98.
de la Rosa P, Barnett JB, Schafer R. Characterization of thymic atrophy and the mechanism of thymocyte depletion after in vivo exposure to a mixture of herbicides. J Toxicol Environ Health Part A. 2005;68(2):81-98.
de la Rosa, P., Barnett, J. B., & Schafer, R. (2005). Characterization of thymic atrophy and the mechanism of thymocyte depletion after in vivo exposure to a mixture of herbicides. Journal of Toxicology and Environmental Health. Part A, 68(2), 81-98.
de la Rosa P, Barnett JB, Schafer R. Characterization of Thymic Atrophy and the Mechanism of Thymocyte Depletion After in Vivo Exposure to a Mixture of Herbicides. J Toxicol Environ Health Part A. 2005 Jan 22;68(2):81-98. PubMed PMID: 15762548.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of thymic atrophy and the mechanism of thymocyte depletion after in vivo exposure to a mixture of herbicides. AU - de la Rosa,Patricia, AU - Barnett,John B, AU - Schafer,Rosana, PY - 2005/3/15/pubmed PY - 2005/4/1/medline PY - 2005/3/15/entrez SP - 81 EP - 98 JF - Journal of toxicology and environmental health. Part A JO - J. Toxicol. Environ. Health Part A VL - 68 IS - 2 N2 - 3,4-Dichloropropionanilide (propanil) and 2,4-dichlorophenoxyacetic acid (2,4-D) are two commonly used herbicides that are marketed as a chemical mixture. It was hypothesized that the interaction between these two herbicides, when administered as a mixture, would result in a greater effect on the immune system than the individual components of the mixture. The present study demonstrates in a murine model that a mixture of propanil and 2,4-D, when compared to single herbicide exposures, exacerbates decreases in thymocyte populations 2 d postexposure and inhibits the repopulation of T-cells in the thymus 7 d postexposure. Exposure to 150 mg herbicide/kg body weight of propanil or 2,4-D alone had no effect on thymus weight. In contrast, decreases in the ratio of thymus weight to body weight (TW:BW) occurred 2 d after treatment with the mixture of 150 mg propanil/kg body weight + 150 mg 2,4-D/kg body weight (150/150). Thymic atrophy was associated with a decrease in the double-positive thymocyte population (CD4+CD8+) and correlated with sera corticosterone levels from 600 to 1000 pg/ml. Therefore, the hypothesis was tested that glucocorticoids, induced after exposure to herbicides, were responsible for the thymic atrophy and depletion of thymocytes. However, similar levels of corticosterone were induced after exposure to 50, 100, or 150 mg propanil/kg body weight, and 50/50 or 100/100 mixture treatments, doses that did not produce thymic atrophy or cell loss. In addition, RU 486, a glucocorticoid receptor blocker, only partially abrogated the thymic atrophy in mice exposed to the 150/150 mixture of herbicides. These results suggest that glucocorticoids are only partially responsible for herbicide-induced thymic atrophy. This study demonstrates that the effects of exposure to a mixture of chemicals cannot always be predicted based on single exposure data and emphasizes the importance of mixture-based studies. SN - 1528-7394 UR - https://www.unboundmedicine.com/medline/citation/15762548/Characterization_of_thymic_atrophy_and_the_mechanism_of_thymocyte_depletion_after_in_vivo_exposure_to_a_mixture_of_herbicides_ L2 - http://www.tandfonline.com/doi/full/10.1080/15287390590886072 DB - PRIME DP - Unbound Medicine ER -