Rat Thymocyte Apoptosis and Proliferation Variations in Chronic Exposure to Low-Dose Dichlorodiphenyltrichloroethane
The aim of the investigation was to study apoptosis and proliferation of rat thymocytes when exposed to low-dose dichlorodiphenyltrichloroethane (DDT) provided for by its maximum allowable level in food products.
Materials and Methods. The experiment was carried out on 64 Wistar male rats administered DDT at doses of 1.890±0.086 and 7.77±0.17 µg/kg/day within 6 and 10 weeks. We performed a histological study of thymus preparations, immunohistochemistry of pro-apoptotic proteins Bax and p53, the assessment of the proliferative activity of thymocytes by a radionuclide method, and the corticosterone and interleukin-2 concentrations in rat blood serum using an enzyme immunoassay.
Results. The study of thymus of control and experimental rats 6 weeks after the experiment start showed the selected doses of DDT to activate the synthesis of pro-apoptotic proteins and initiate p53-dependent apoptosis of both low- and high-grade differentiated thymocytes resulting in focal depletion of thymic cortex. It causes a reactive increase of interleukin-2 production and thymocyte proliferation, however, results in no thymocyte population recovery. Subsequently, with DDT accumulation and exposure time increase, there is the enhanced death of both lymphocytes and reticular epithelial cells, and proliferative activity of thymocytes is suppressed despite the decreased secretion of glucocorticosteroids by adrenals, it being the basic acceleration mechanism of observable involutory changes of thymus.
- Bachman M.J., Keller J.M., West K.L., Jensen B.A. Persistent organic pollutant concentrations in blubber of 16 species of cetaceans stranded in the Pacific Islands from 1997 through 2011. Sci Total Environ 2014; 488–489: 115–123, https://doi.org/10.1016/j.scitotenv.2014.04.073.
- Velasco A., Hernández S., Ramírez M., Ortíz I. Detection of residual organochlorine and organophosphorus pesticides in agricultural soil in Rio Verde region of San Luis Potosi, Mexico. J Environ Sci Health B 2014; 49(7): 498–504, https://doi.org/10.1080/03601234.2014.896670.
- Bouwman H., Booyens P., Govender D., Pienaar D., Polder A. Chlorinated, brominated, and fluorinated organic pollutants in Nile crocodile eggs from the Kruger National Park, South Africa. Ecotoxicol Environ Saf 2014; 104: 393–402, https://doi.org/10.1016/j.ecoenv.2013.12.005.
- Gigienicheskie trebovaniya bezopasnosti i pishchevoy tsennosti pishchevykh produktov. SanPin 2.3.2.1078-01 [Hygienic safety and nutrition value requirements of food products. Sanitary Regulations and Norms 2.3.2.1078-01]. 2008.
- Yaglova N.V., Obernikhin S.S. The influence of maternal immune system activation in early pregnancy on offspring immune system development. Problemy reproduktsii 2013; 19(1): 73–77.
- Takai K., Shiraishi K., Fujikawa K., Hiragino T., Konishi M., Aoki A., Suga A., Fujimoto M., Nakamura K., Naito K. Effects of glucocorticoids on rat thymus and apoptosis. Transplant Proc 2000; 32(7): 2082–2085, https://doi.org/10.1016/s0041-1345(00)01578-5.
- Lin’kova N.S., Polyakova V.O., Kvetnoy I.M. The relationship of thymocyte apoptosis and proliferation in thymolysis. Byulleten’ eksperimental’noy biologii i meditsiny 2011; 151(4): 442–444.
- Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol 2007; 35(4): 495–516, https://doi.org/10.1080/01926230701320337.
- Porter B.O., Malek T.R. Thymic and intestinal intraepithelial T lymphocyte development are each regulated by the gammac-dependent cytokines IL-2, IL-7, and IL-15. Semin Immunol 2000; 12(5): 465–474, https://doi.org/10.1006/smim.2000.0264.
- Liao W., Lin J.-X., Leonard W.J. IL-2 family cytokines: new insights into the complex roles of IL-2 as a broad regulator of T helper cell differentiation. Curr Opin Immunol 2011; 23(5): 598–604, http://dx.doi.org/10.1016/j.coi.2011.08.003.
- Shanley D.P., Aw D., Manley N.R., Palmer D.B. An evolutionary perspective on the mechanisms of immunosenescence. Trends Immunol 2009; 30(7): 374–381, https://doi.org/10.1016/j.it.2009.05.001.
- Rodichenko E.P., Yaglova N.V., Yaglov V.V., Obernikhin S.S. Changes in rat thymus morphology and function after chronic exposure to low doses of DDT. Rossiyskiy mediko-biologicheskiy vestnik im. akademika I.P. Pavlova 2013; 2: 36–41.
- Yaglova N.V., Timokhina E.P., Yaglov V.V. Effects of low-dose dichlorodiphenyltrichloroethane on the morphology and function of rat thymus. Bull Exp Biol Med 2013; 155(5): 701–704, https://doi.org/10.1007/s10517-013-2230-1 .