Polycyclic aromatic hydrocarbon diol epoxides increase cytosolic Ca2+ of airway epithelial cells

Polycyclic aromatic hydrocarbons (PAHs) increase cytosolic Ca2+ concentrati on ([Ca2+](i)) in lymphocytes and mammary epithelial cells, but little is k nown regarding their effects on [Ca2+](i) in airway epithelium. We hypothes ized that benzo[a]pyrene (BP) and/or anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10 -tetrahydro-benzo[a]pyrene (BPDE), a carcinogenic BP metabolite, increases [Ca2+](i) in untransformed human small airway epithelial (SAE) cells and th at their effects on [Ca2+](i) are directly proportional to carcinogenicity. SAE [Ca2+](i) was determined by a ratiometric digital Ca2+ imaging system. BPDE increased SAE [Ca2+](i) within 20 s in media with high (1 mM) and low (10 nM) Ca2+ at a threshold concentration of 0.2 nM. Elevation of [Ca2+](i ) persisted longer with high Ca2+. Neither BP nor solvent altered [Ca2+](i) . Thapsigargin and inositol 1,4 5- phosphate receptor (InsP(3)R) antagonist s inhibited this BPDE action with low Ca2+. We conclude that BPDE but not B P increases [Ca2+](i) partly by mobilizing Ca2+ from cytosolic stores throu gh an InsP(3R). The most potent carcinogenic PAH diol epoxide increased in SAE [Ca2+](i) at the lowest threshold concentration, suggesting that carcin ogenicity is directly proportional to the action of PAHs on SAE [Ca2+](i). Short-term exposure to BPDE 36 to 48 h before the study rendered SAE cells less sensitive to BPDE suggesting that BPDE may also induce persistent chan ges in Ca2+ signaling pathways.