Depletion of glutathione by benzo(a)pyrene metabolites, ionomycin, thapsigargin, and phorbol myristate in human peripheral blood mononuclear cells

Toxicology and Applied Pharmacology
D L RomeroS W Burchiel

Abstract

Previous studies in this laboratory have shown that polycyclic aromatic hydrocarbons (PAHs) alter Ca2+ homeostasis and inhibit activation of both B and T lymphocytes obtained from rodents and humans. In the present studies, we demonstrate that alpha-naphthoflavone (ANF), an inhibitor of cytochrome P4501A activity, reduced the Ca2+ elevation produced by BaP in human peripheral blood mononuclear cell (HPBMC) lymphocytes. These results suggested that BaP metabolites may play a role in intracellular Ca2+ homeostasis in human lymphocytes. Reactive oxidative intermediates of BaP produced in HPMBC are known to be highly carcinogenic and have also been shown to be immunosuppressive. We examined the effects of benzo(a)pyrene (BaP), 7,12-dimethylbenz(a)anthracene (DMBA), benzo(e)pyrene (BeP), and anthracene, as well as certain BaP metabolites, on the levels of intracellular Ca2+ and glutathione in HPBMC. While BaP, DMBA, BeP, and anthracene did not cause a statistically significant decrease in GSH in HPBMC at concentrations of 1 or 10 microM following a 6-, 48-, or 72-hr exposure, reactive BaP metabolites including 4,5-epoxide BaP and 7,8-diol-9,10-epoxide BaP consistently produced a 20-30% depletion of glutathione in HPBMC following a 6...Continue Reading

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Citations

Feb 9, 2002·Environmental Health Perspectives·David O CarpenterDavid C Spink
Jul 4, 2009·Toxicology and Applied Pharmacology·Mario T SchellenbergerClaude P Muller
May 25, 2012·Proteomics·Nisha VermaSimone Schmitz-Spanke
Nov 21, 2014·Environmental Science and Pollution Research International·Atif KamalRiffat Naseem Malik
Nov 22, 2014·Toxicological Sciences : an Official Journal of the Society of Toxicology·Nishad JayasundaraRichard T Di Giulio
Aug 8, 2013·International Journal of Toxicology·Kimberly J Zaccaria, Peter R McClure
Oct 30, 2004·International Journal of Toxicology·Aramandla RameshEric H Weyand
May 13, 1999·Immunopharmacology and Immunotoxicology·J W RodriguezP Urso
Nov 24, 2011·Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews·Deacqunita L DiggsAramandla Ramesh
Apr 6, 2017·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·Vasco BrancoCristina Carvalho
Aug 17, 2004·Annals of Saudi Medicine·Bekir CoksevimMehtap Türk
Oct 23, 2001·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·A RameshA M Nyanda

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