Induction of PreB cell apoptosis by 7,12-dimethylbenz[a]anthracene in long-term primary murine bone marrow cultures

Toxicology and Applied Pharmacology
K YamaguchiDavid H Sherr

Abstract

Numerous studies demonstrate that polycyclic aromatic hydrocarbons (PAH) suppress immunity by modifying the function of both B and T cells. Relatively few studies have assessed the effects of these common environmental chemicals on immature lymphocytes. In the present study, long-term primary bone marrow cultures were employed to investigate the effects of a prototypic PAH and aryl hydrocarbon receptor (AhR) agonist, 7,12-dimethylbenz[a]anthracene (DMBA), on immature B lymphocytes. In this system, immature preB cells are maintained in a supportive microenvironment provided by bone marrow stromal cells. Results presented here demonstrate that (1) exposure of primary bone marrow cultures to DMBA results in preB cell death by apoptosis; (2) notably low doses of DMBA (> or = 10(-8) M) induce preB cell apoptosis; (3) in long-term cultures, bone marrow stromal cells, but not preB cells, express AhR mRNA and protein as determined by in situ hybridization, RT-PCR, and immunoblotting; (4) freshly isolated unfractionated bone marrow cells, but not purified bone marrow B cells, express AhR protein as assessed by immunohistochemistry; (5) alpha-naphthoflavone, a competitive AhR inhibitor and cytochrome P450 antagonist, completely blocks DM...Continue Reading

Citations

Aug 15, 2013·Seminars in Immunopathology·David H Sherr, Stefano Monti
Sep 3, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Stephanie L BissonnetteJennifer J Schlezinger
Dec 18, 2003·Environmental Health : a Global Access Science Source·Brenda A JensenDavid H Sherr
Mar 26, 2010·Environmental Health : a Global Access Science Source·Lenka L Allan, David H Sherr
Feb 14, 2006·Biochemical and Biophysical Research Communications·Lenka L AllanDavid H Sherr
Apr 12, 2017·Toxicological Sciences : an Official Journal of the Society of Toxicology·Amelia H BakerJennifer J Schlezinger
Aug 20, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jessica E TeagueJennifer J Schlezinger
Dec 10, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jennifer J SchlezingerDavid H Sherr
May 8, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Heui-Young RyuDavid H Sherr
Mar 25, 2019·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Ligia Lins de CastroPatricia Rieken Macêdo Rocco
Mar 9, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Béatrice LaupezeOlivier Fardel
Dec 20, 2018·International Journal of Molecular Sciences·Necola GuerrinaCarolyn J Baglole

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis