Characterization of Intracellular Calcium Responses Produced by Polycyclic Aromatic Hydrocarbons in Surface Marker-Defined Human Peripheral Blood Mononuclear Cells

• Published in: Toxicology and applied pharmacology Vol. 145; no. 2; pp. 323 - 330
• Main Authors: Mounho, Barbara J., Davila, Donna R., Burchiel, Scott W.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.08.1997; Elsevier
• Subjects: 9,10-Dimethyl-1,2-benzanthracene - blood; 9,10-Dimethyl-1,2-benzanthracene - toxicity; Adult; Antigens, CD - analysis; B-Lymphocyte Subsets - drug effects; B-Lymphocyte Subsets - metabolism; Benzo(a)pyrene - metabolism; Benzo(a)pyrene - toxicity; Biological and medical sciences; Calcium - blood; Calcium - metabolism; Chemical and industrial products toxicology. Toxic occupational diseases; Humans; Immunosuppressive Agents - toxicity; Intracellular Fluid - drug effects; Intracellular Fluid - metabolism; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Medical sciences; Polycyclic Aromatic Hydrocarbons - blood; Polycyclic Aromatic Hydrocarbons - toxicity; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - metabolism; Time Factors; Toxicology; Various organic compounds; Human; Immunopathology; Monocyte; Toxicity; Cytochrome P450; Metabolism toxicity relation; B-Lymphocyte; Calcium Ions; Polycyclic aromatic compound; In vitro; Immunosuppression; Mononuclear cell; T-Lymphocyte; Intracellular; Mechanism of action
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1006/taap.1997.8182

Previous studies have demonstrated that polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP) and 7,12-dimethybenz[a]anthracene (DMBA), and possibly 2,3,7,8-tetrachlorodibenzo(p)dioxin (TCDD), may exert their immunosuppressive effects by altering intracellular Ca2+homeostasis in lymphocytes. In these studies, we examined the effects of two immunosuppressive PAHs (BaP and DMBA), two nonimmunosuppressive PAHs (benzo[e]pyrene (BeP) and anthracene (ANTH)), and TCDD on intracellular Ca2+levels in surface marker-defined human peripheral blood mononuclear cells (HPBMC). BaP and DMBA, but not BeP and ANTH, were found to produce a time-dependent increase in intracellular Ca2+with maximal effects achieved following 42- to 66-hr exposures. In a series of studies with HPBMC obtained from 10 donors exposedin vitrofor 42 hr, BaP and DMBA were found to produce a significant increase in Ca2+in CD3+T cells, CD19+B cells, and CD14+monocytes. BeP and ANTH did not produce a statistically significant increase in Ca2+in the group of donors, but occasionally produced an apparent nonspecific elevation of Ca2+in HPBMC from individual donors. Interestingly, TCDD produced a small and statistically significant increase in Ca2+only in B cells analyzed for the pooled 10 donors. Certain BaP metabolites, such as the 7,8-dihydrodiol and the 7,8-diol-9,10-epoxide, were more effective in elevating Ca2+in HPBMC lymphocytes at 20 hr than was BaP. These results demonstrate in normal HPBMC that immunosuppressive PAHs alter intracellular Ca2+homeostasis in B cells, T cells, and monocytes, and suggest that P450 metabolism may play an important role in the immunotoxicity of certain PAHs.