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Effects of Xenoestrogens on T Lymphocytes: Modulation of bcl-2, p53, and Apoptosis
Molecular Toxicology Research Laboratory, Jackson State University, NIH-Center for Environmental Health, School of Science and Technology, 1400 Lynch Street, Box 18540, Jackson, Mississippi 39217, USA
Rheumatology Section, G.V. (Sonny) Montgomery V.A. Hospital, University of Mississippi School of Medicine, 2500 North State Street, Jackson, MS 39216, USA
Division of Rheumatology and Molecular Immunology, L525 Clinical Sciences Building, University of Mississippi School of Medicine, 2500 North State Street, Jackson, MS 39216, USA
* Author to whom correspondence should be addressed.
Received: 7 June 2002 / Accepted: 30 October 2002 / Published: 31 January 2003
Abstract: Endogenous estrogens have significant immunomodulatory effects characterized as suppression of cell mediated immunity and stimulation of humoral immunity. Xenoestrogens are environmental estrogens that have endocrine impact, acting as estrogen agonists and antagonists but whose immune effects are not well characterized. Using CD4+ Jurkat T cells as a model, the effects of representative xenoestrogens on T proliferation, cell cycle, and apoptosis were examined. Coumestrol (CM), a phytoestrogen, and tetrachlorodioxin (TCDD) in concentrations of 10-4 to 10-6M significantly inhibited Jurkat T cell lymphoproliferation, whereas bisphenol A (BPA) and DDT had minimal effect, but did antagonize 17-β-estrtadiol induced effects. Xenoestrogens, especially CM, produced accumulation of Jurkat T cells in G2/M phase, and subsequently induced apoptosis, particularly CM (% apoptotic cells = 30 ± 12 vs. control = 5 ± 2). These changes were associated with DNA fragmentation. BPA and DDT also induced DNA fragmentation but not significant DNA hypoploidy. Xenoestrogen – CM, BPA, DDT, and TCDD - exposure suppressed bcl-2 protein and mRNA transcript levels but augmented p53 protein and mRNA transcripts. Human purified peripheral blood lymphocytes responded with similar significant cell cycle changes (G0/G1 exodus and G2/M accumulation) for CM, BPA, and DDT exposure. These preliminary data, taken together, suggest that xenoestrogens have direct, compound-specific T lymphocyte effects that enhance our understanding of environmental modulation of immune and autoimmune responses.
Keywords: Xenoestrogens; coumestrol; bisphenol A; DDT; TCDD; T lymphocytes; cell cycle
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Ndebele, K.; Tchounwou, P.B.; McMurray, R.W. Effects of Xenoestrogens on T Lymphocytes: Modulation of bcl-2, p53, and Apoptosis. Int. J. Mol. Sci. 2003, 4, 45-61.
Ndebele K, Tchounwou PB, McMurray RW. Effects of Xenoestrogens on T Lymphocytes: Modulation of bcl-2, p53, and Apoptosis. International Journal of Molecular Sciences. 2003; 4(2):45-61.
Ndebele, Kenneth; Tchounwou, Paul B.; McMurray, Robert W. 2003. "Effects of Xenoestrogens on T Lymphocytes: Modulation of bcl-2, p53, and Apoptosis." Int. J. Mol. Sci. 4, no. 2: 45-61.