{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T17:07:43Z","timestamp":1784740063855,"version":"3.55.0"},"reference-count":72,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2009,8,5]],"date-time":"2009-08-05T00:00:00Z","timestamp":1249430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cytometry Pt A"],"published-print":{"date-parts":[[2009,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cigarette smoke (CS) is a major cause of lung cancer and a contributor to the development of a wide range of other malignancies. There is an acute need to develop a methodology that can rapidly assess the potential carcinogenic properties of the genotoxic agents present in CS. We recently reported that exposure of normal human bronchial epithelial cells (NHBEs) or A549 pulmonary carcinoma cells to CS induces the activation of ATM through its phosphorylation on <jats:italic>Ser<\/jats:italic>1981 and phosphorylation of histone H2AX on <jats:italic>Ser139<\/jats:italic> (\u03b3H2AX) most likely in response to the formation of potentially carcinogenic DNA double\u2010strand breaks (DSBs). To obtain a more complete view of the DNA damage response (DDR) we explored the correlation between ATM activation, H2AX phosphorylation, activation of Chk2 through its phosphorylation on <jats:italic>Thr<\/jats:italic>68, and phosphorylation of p53 on <jats:italic>Ser<\/jats:italic>15 in NHBE and A549 cell exposed to CS. Multiparameter analysis by laser scanning cytometry made it possible to relate these DDR events, detected immunocytochemically, with cell cycle phase. The CS\u2010dose\u2010dependent induction and increase in the extent of phosphorylation of ATM, Chk2, H2AX, and p53 were seen in both cell types. ATM and Chk2 were phosphorylated \u223c1 h prior to phosphorylation of H2AX and p53. The dephosphorylation of ATM, Chk2, and H2AX was seen after 2 h following CS exposure. The dose\u2010dependency and kinetics of DDR were essentially similar in both cell types, which provide justification for the use of A549 cells in the assessment of genotoxicity of CS in lieu of normal bronchial epithelial cells. The observation that DDR was more pronounced in S\u2010phase cells is consistent with the mechanism of induction of DSBs occurring as a result of collision of replication forks with primary lesions such as DNA adducts that can be caused by CS\u2010generated oxidants. The cytometric assessment of CS\u2010induced DDR provides a means to estimate the genotoxicity of CS and to explore the mechanisms of the response as a function of cell cycle phase and cell type. \u00a9 2009 International Society for Advancement of Cytometry<\/jats:p>","DOI":"10.1002\/cyto.a.20778","type":"journal-article","created":{"date-parts":[[2009,8,5]],"date-time":"2009-08-05T18:30:53Z","timestamp":1249497053000},"page":"840-847","source":"Crossref","is-referenced-by-count":55,"title":["DNA damage response induced by tobacco smoke in normal human bronchial epithelial and A549 pulmonary adenocarcinoma cells assessed by laser scanning cytometry"],"prefix":"10.1002","volume":"75A","author":[{"given":"Hong","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony 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