Polycyclic aromatic hydrocarbon diol epoxides increase cytosolic Ca(2+) of airway epithelial cells.
Polycyclic aromatic hydrocarbons (PAHs) increase cytosolic Ca(2+) concentration ([Ca(2+)](i)) in lymphocytes and mammary epithelial cells, but little is known regarding their effects on [Ca(2+)](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 [Ca(2+)](i) in untransformed human small airway epithelial (SAE) cells and that their effects on [Ca(2+)](i) are directly proportional to carcinogenicity. SAE [Ca(2+)](i) was determined by a ratiometric digital Ca(2+) imaging system. BPDE increased SAE [Ca(2+)](i) within 20 s in media with high (1 mM) and low (10 nM) Ca(2+) at a threshold concentration of 0.2 nM. Elevation of [Ca(2+)](i) persisted longer with high Ca(2+). Neither BP nor solvent altered [Ca(2+)](i). Thapsigargin and inositol 1,4,5- phosphate receptor (InsP(3)R) antagonists inhibited this BPDE action with low Ca(2+). We conclude that BPDE but not BP increases [Ca(2+)](i) partly by mobilizing Ca(2+) from cytosolic stores through an InsP(3)R. The most potent carcinogenic PAH diol epoxide increased in SAE [Ca(2+)](i) at the lowest threshold concentration, suggesting that carcinogenicity is directly proportional to the action of PAHs on SAE [Ca(2+)](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 Ca(2+) signaling pathways.
Jyonouchi
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Department of Pediatrics, School of Medicine, University of Minnesota, 420 Delaware St. SE, Minneapolis, MN 55455, USA. jyono001@tc.umn.edu
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Porter
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D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism*; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D003600:Cytosol / Q000187:drug effects* / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D014132:Trachea / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D002273:Carcinogens; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D002118:Calcium