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Am. J. Respir. Cell Mol. Biol., Volume 25, Number 1, July, 2001 78-83

Polycyclic Aromatic Hydrocarbon Diol Epoxides Increase Cytosolic Ca2+ of Airway Epithelial Cells

Harumi Jyonouchi, Sining Sun, Valerie A. Porter, and David N. Cornfield

Department of Pediatrics, School of Medicine, University of Minnesota, Minneapolis, Minnesota

Polycyclic aromatic hydrocarbons (PAHs) increase cytosolic Ca2+ concentration ([Ca2+]i) in lymphocytes and mammary epithelial cells, but little is known regarding their effects on [Ca2+]i in airway epithelium. We hypothesized that benzo[a]pyrene (BP) and/or anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE), a carcinogenic BP metabolite, increases [Ca2+]i in untransformed human small airway epithelial (SAE) cells and that 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 (InsP3R) antagonists inhibited this BPDE action with low Ca2+. We conclude that BPDE but not BP increases [Ca2+]i partly by mobilizing Ca2+ from cytosolic stores through an InsP3R. The most potent carcinogenic PAH diol epoxide increased in SAE [Ca2+]i at the lowest threshold concentration, suggesting that carcinogenicity 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 changes in Ca2+ signaling pathways.

Abbreviations: 2-aminoethosydiphenyl borate, 2-APB; arylhydrocarbon receptor, AhR; anti-3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene, BcPDE; benzo[a]pyrene, BP; anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene, BPDE; cytosolic CA2+ concentration, [Ca2+]i; dimethyl sulfoxide, DMSO; extracellular regulated kinase, Erk; inositol 1,4,5-triphosphate receptor, InsP3R; anti-1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene, 5MeCDE; anti-1,2-dihydroxy-3,4-epoxy-1,2, 3,4-tetrahydro-6-methylchrysene, 6MeCDE; polycyclic aromatic hydrocarbon, PAH; small airway epithelial, SAE; xestospongin C, Xest C.




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Copyright © 2001 American Thoracic Society.