CHARACTERIZATION OF INTRACELLULAR CALCIUM RESPONSES PRODUCED BY POLYCYCLIC AROMATIC-HYDROCARBONS IN SURFACE MARKER-DEFINED HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS

Previous studies have demonstrated that polycyclic aromatic hydrocarbo ns (PAHs), such as benzo[a]pyrene (BaP) and 7,12-dimethybenz[a]anthrac ene (DMBA), and possibly 2,3,7,8-tetrachlorodibenzo(p)dioxin (TCDD), m ay exert their immunosuppressive effects by altering intracellular Ca2 + homeostasis in lymphocytes. In these studies, we examined the effect s of two immunosuppressive PAHs (BaP and DMBA), two nonimmunosuppressi ve PAHs (benzo[e]pyrene (BeP) and anthracene (ANTH)), and TCDD on intr acellular Ca2+ levels in surface marker-defined human peripheral blood mononuclear cells (HPBMC). BaP and DMBA, but not BeP and ANTH, were f ound to produce a time-dependent increase in intracellular Ca2+ with m aximal effects achieved following 42- to 66-hr exposures. In a series of studies with HPBMC obtained from 10 donors exposed in vitro for 42 hr, BaP and DMBA were found to produce a significant increase in Ca2in CD3+ T cells, CD19(+) B cells, and CD14(+) monocytes. BeP and ANTH did not produce a statistically significant increase in Ca2+ in the gr oup of donors, but occasionally produced an apparent nonspecific eleva tion of Ca2+ in HPBMC from individual donors. Interestingly, TCDD prod uced 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 effec tive in elevating Ca2+ in HPBMC lymphocytes at 20 hr than was BaP. The se results demonstrate in normal HPBMC that immunosuppressive PAHs alt er intracellular Ca2+ homeostasis in B cells, T cells, and monocytes, and suggest that P450 metabolism may play an important role in the imm unotoxicity of certain PAHs. (C) 1997 Academic Press.