{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:17:02Z","timestamp":1773793022892,"version":"3.50.1"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Hematol Oncol"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Given potential values of induced pluripotent stem (iPS) cells in basic biomedical research and regenerative medicine, it is important to understand how these cells regulate their genome stability in response to environmental toxins and carcinogens. The present study characterized the effect of Cr(VI), a well-known genotoxic agent and environmental carcinogen, on major molecular components of DNA damage response pathways in human iPS cells. We compared the effect of Cr(VI) on human iPS cells with two established cell lines, Tera-1 (teratoma origin) and BEAS-2B (lung epithelial origin). We also studied the effect of hydrogen peroxide and doxorubicin on modulating DNA damage responses in these cell types. We demonstrated that ATM and p53 phosphorylation is differentially regulated in human iPS cells compared with Tera-1 and BEAS-2B cells after exposure to various genotoxic agents. Moreover, we observed that inhibition of CK2, but not p38, promotes phosphorylation of p53<jats:sup>S392<\/jats:sup> in iPS cells. Combined, our data reveal some unique features of DNA damage responses in human iPS cells.<\/jats:p>","DOI":"10.1186\/1756-8722-6-71","type":"journal-article","created":{"date-parts":[[2013,9,20]],"date-time":"2013-09-20T16:28:05Z","timestamp":1379694485000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Differential responses to genotoxic agents between induced pluripotent stem cells and tumor cell lines"],"prefix":"10.1186","volume":"6","author":[{"given":"Yinghua","family":"Lu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dazhong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yupo","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongping","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenxian","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,9,20]]},"reference":[{"issue":"5","key":"340_CR1","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","volume":"131","author":"K Takahashi","year":"2007","unstructured":"Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K: Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007, 131 (5): 861-872. 10.1016\/j.cell.2007.11.019.","journal-title":"Cell"},{"issue":"7381","key":"340_CR2","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/nature10761","volume":"481","author":"DA Robinton","year":"2012","unstructured":"Robinton DA, Daley GQ: The promise of induced pluripotent stem cells in research and therapy. Nature. 2012, 481 (7381): 295-305. 10.1038\/nature10761.","journal-title":"Nature"},{"issue":"4","key":"340_CR3","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/j.stem.2013.01.009","volume":"12","author":"T Kondo","year":"2013","unstructured":"Kondo T, Asai M, Tsukita K, Kutoku Y, Ohsawa Y, Sunada Y: Modeling Alzheimer\u2019s disease with iPSCs reveals stress phenotypes associated with intracellular abeta and differential drug responsiveness. Cell Stem Cell. 2013, 12 (4): 487-496. 10.1016\/j.stem.2013.01.009.","journal-title":"Cell Stem Cell"},{"key":"340_CR4","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/1756-8722-4-54","volume":"4","author":"D Xu","year":"2011","unstructured":"Xu D, TM O, Shartava A, Fowles TC, Yang J, Fink LM: Isolation, characterization, and in vitro propagation of infantile hemangioma stem cells and an in vivo mouse model. J Hematol Oncol. 2011, 4: 54-10.1186\/1756-8722-4-54.","journal-title":"J Hematol Oncol"},{"key":"340_CR5","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/1756-8722-4-38","volume":"4","author":"J Yang","year":"2011","unstructured":"Yang J, Aguila JR, Alipio Z, Lai R, Fink LM, Ma Y: Enhanced self-renewal of hematopoietic stem\/progenitor cells mediated by the stem cell gene Sall4. J Hematol Oncol. 2011, 4: 38-10.1186\/1756-8722-4-38.","journal-title":"J Hematol Oncol"},{"issue":"11","key":"340_CR6","doi-asserted-by":"publisher","first-page":"2475","DOI":"10.1093\/carcin\/15.11.2475","volume":"15","author":"X Shi","year":"1994","unstructured":"Shi X, Mao Y, Knapton AD, Ding M, Rojanasakul Y, Gannett PM: Reaction of Cr(VI) with ascorbate and hydrogen peroxide generates hydroxyl radicals and causes DNA damage: role of a Cr(IV)-mediated Fenton-like reaction. Carcinogenesis. 1994, 15 (11): 2475-2478. 10.1093\/carcin\/15.11.2475.","journal-title":"Carcinogenesis"},{"issue":"1\u20132","key":"340_CR7","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1023\/B:MCBI.0000007274.25052.82","volume":"255","author":"A Chiu","year":"2004","unstructured":"Chiu A, Katz AJ, Beaubier J, Chiu N, Shi X: Genetic and cellular mechanisms in chromium and nickel carcinogenesis considering epidemiologic findings. Mol Cell Biochem. 2004, 255 (1\u20132): 181-194.","journal-title":"Mol Cell Biochem"},{"issue":"1\u20132","key":"340_CR8","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1023\/A:1015975218920","volume":"234-235","author":"M Ding","year":"2002","unstructured":"Ding M, Shi X: Molecular mechanisms of Cr(VI)-induced carcinogenesis. Mol Cell Biochem. 2002, 234-235 (1\u20132): 293-300.","journal-title":"Mol Cell Biochem"},{"issue":"2","key":"340_CR9","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1002\/ajim.4700170205","volume":"17","author":"S Langard","year":"1990","unstructured":"Langard S: One hundred years of chromium and cancer: a review of epidemiological evidence and selected case reports. Am J Ind Med. 1990, 17 (2): 189-215. 10.1002\/ajim.4700170205.","journal-title":"Am J Ind Med"},{"issue":"7","key":"340_CR10","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1289\/ehp.0800157","volume":"117","author":"L Chen","year":"2009","unstructured":"Chen L, Ovesen JL, Puga A, Xia Y: Distinct contributions of JNK and p38 to chromium cytotoxicity and inhibition of murine embryonic stem cell differentiation. Environ Health Perspect. 2009, 117 (7): 1124-1130.","journal-title":"Environ Health Perspect"},{"issue":"10","key":"340_CR11","doi-asserted-by":"publisher","first-page":"e13410","DOI":"10.1371\/journal.pone.0013410","volume":"5","author":"O Momcilovic","year":"2010","unstructured":"Momcilovic O, Knobloch L, Fornsaglio J, Varum S, Easley C, Schatten G: DNA damage responses in human induced pluripotent stem cells and embryonic stem cells. PLoS One. 2010, 5 (10): e13410-10.1371\/journal.pone.0013410.","journal-title":"PLoS One"},{"key":"340_CR12","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1146\/annurev.genet.40.110405.090428","volume":"40","author":"TT Su","year":"2006","unstructured":"Su TT: Cellular responses to DNA damage: one signal, multiple choices. Annu Rev Genet. 2006, 40: 187-208. 10.1146\/annurev.genet.40.110405.090428.","journal-title":"Annu Rev Genet"},{"issue":"10","key":"340_CR13","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/nrc2716","volume":"9","author":"DW Meek","year":"2009","unstructured":"Meek DW: Tumour suppression by p53: a role for the DNA damage response?. Nat Rev Cancer. 2009, 9 (10): 714-723.","journal-title":"Nat Rev Cancer"},{"key":"340_CR14","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1007\/978-1-61779-998-3_40","volume":"920","author":"A Sharma","year":"2012","unstructured":"Sharma A, Singh K, Almasan A: Histone H2AX phosphorylation: a marker for DNA damage. Methods Mol Biol. 2012, 920: 613-626. 10.1007\/978-1-61779-998-3_40.","journal-title":"Methods Mol Biol"},{"issue":"12","key":"340_CR15","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1038\/nrc2012","volume":"6","author":"F Toledo","year":"2006","unstructured":"Toledo F, Wahl GM: Regulating the p53 pathway: in vitro hypotheses, in vivo veritas. Nat Rev Cancer. 2006, 6 (12): 909-923. 10.1038\/nrc2012.","journal-title":"Nat Rev Cancer"},{"issue":"4","key":"340_CR16","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1016\/j.cell.2009.04.050","volume":"137","author":"JP Kruse","year":"2009","unstructured":"Kruse JP, Gu W: Modes of p53 regulation. Cell. 2009, 137 (4): 609-622. 10.1016\/j.cell.2009.04.050.","journal-title":"Cell"},{"issue":"56","key":"340_CR17","doi-asserted-by":"publisher","first-page":"7741","DOI":"10.1038\/sj.onc.1210872","volume":"26","author":"JH Lee","year":"2007","unstructured":"Lee JH, Paull TT: Activation and regulation of ATM kinase activity in response to DNA double-strand breaks. Oncogene. 2007, 26 (56): 7741-7748. 10.1038\/sj.onc.1210872.","journal-title":"Oncogene"},{"issue":"11","key":"340_CR18","doi-asserted-by":"publisher","first-page":"5298","DOI":"10.1182\/blood-2007-10-117622","volume":"111","author":"N Takayama","year":"2008","unstructured":"Takayama N, Nishikii H, Usui J, Tsukui H, Sawaguchi A, Hiroyama T: Generation of functional platelets from human embryonic stem cells in vitro via ES-sacs, VEGF-promoted structures that concentrate hematopoietic progenitors. Blood. 2008, 111 (11): 5298-5306. 10.1182\/blood-2007-10-117622.","journal-title":"Blood"},{"issue":"8","key":"340_CR19","first-page":"2891","volume":"36","author":"RL Momparler","year":"1976","unstructured":"Momparler RL, Karon M, Siegel SE, Avila F: Effect of adriamycin on DNA, RNA, and protein synthesis in cell-free systems and intact cells. Cancer Res. 1976, 36 (8): 2891-2895.","journal-title":"Cancer Res"},{"issue":"7","key":"340_CR20","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/S0006-2952(98)00307-4","volume":"57","author":"DA Gewirtz","year":"1999","unstructured":"Gewirtz DA: A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem Pharmacol. 1999, 57 (7): 727-741. 10.1016\/S0006-2952(98)00307-4.","journal-title":"Biochem Pharmacol"},{"issue":"51","key":"340_CR21","doi-asserted-by":"publisher","first-page":"50206","DOI":"10.1074\/jbc.M209820200","volume":"277","author":"DM Keller","year":"2002","unstructured":"Keller DM, Lu H: p53 serine 392 phosphorylation increases after UV through induction of the assembly of the CK2.hSPT16.SSRP1 complex. J Biol Chem. 2002, 277 (51): 50206-50213. 10.1074\/jbc.M209820200.","journal-title":"J Biol Chem"},{"issue":"18","key":"340_CR22","doi-asserted-by":"publisher","first-page":"12229","DOI":"10.1074\/jbc.274.18.12229","volume":"274","author":"C Huang","year":"1999","unstructured":"Huang C, Ma WY, Maxiner A, Sun Y, Dong Z: p38 kinase mediates UV-induced phosphorylation of p53 protein at serine 389. J Biol Chem. 1999, 274 (18): 12229-12235. 10.1074\/jbc.274.18.12229.","journal-title":"J Biol Chem"},{"issue":"3","key":"340_CR23","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1016\/j.cellsig.2009.11.014","volume":"22","author":"ML Cox","year":"2010","unstructured":"Cox ML, Meek DW: Phosphorylation of serine 392 in p53 is a common and integral event during p53 induction by diverse stimuli. Cell Signal. 2010, 22 (3): 564-571. 10.1016\/j.cellsig.2009.11.014.","journal-title":"Cell Signal"},{"issue":"Pt 1","key":"340_CR24","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1042\/bj3510095","volume":"351","author":"SP Davies","year":"2000","unstructured":"Davies SP, Reddy H, Caivano M, Cohen P: Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000, 351 (Pt 1): 95-105.","journal-title":"Biochem J"},{"issue":"Pt 3","key":"340_CR25","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1042\/bj20030674","volume":"374","author":"S Sarno","year":"2003","unstructured":"Sarno S, de Moliner E, Ruzzene M, Pagano MA, Battistutta R, Bain J: Biochemical and three-dimensional-structural study of the specific inhibition of protein kinase CK2 by [5-oxo-5,6-dihydroindolo-(1,2-a)quinazolin-7-yl]acetic acid (IQA). Biochem J. 2003, 374 (Pt 3): 639-646.","journal-title":"Biochem J"},{"issue":"2","key":"340_CR26","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1038\/ng1972","volume":"39","author":"JE Ohm","year":"2007","unstructured":"Ohm JE, McGarvey KM, Yu X, Cheng L, Schuebel KE, Cope L: A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing. Nat Genet. 2007, 39 (2): 237-242. 10.1038\/ng1972.","journal-title":"Nat Genet"},{"issue":"7259","key":"340_CR27","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1038\/nature08287","volume":"460","author":"RM Marion","year":"2009","unstructured":"Marion RM, Strati K, Li H, Murga M, Blanco R, Ortega S: A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity. Nature. 2009, 460 (7259): 1149-1153. 10.1038\/nature08287.","journal-title":"Nature"},{"issue":"5","key":"340_CR28","doi-asserted-by":"publisher","first-page":"519","DOI":"10.4161\/cc.5.5.2514","volume":"5","author":"SK Radhakrishnan","year":"2006","unstructured":"Radhakrishnan SK, Gartel AL: CDK9 phosphorylates p53 on serine residues 33, 315 and 392. Cell Cycle. 2006, 5 (5): 519-521. 10.4161\/cc.5.5.2514.","journal-title":"Cell Cycle"},{"issue":"17","key":"340_CR29","doi-asserted-by":"publisher","first-page":"2690","DOI":"10.1038\/sj.onc.1202620","volume":"18","author":"AR Cuddihy","year":"1999","unstructured":"Cuddihy AR, Wong AH, Tam NW, Li S, Koromilas AE: The double-stranded RNA activated protein kinase PKR physically associates with the tumor suppressor p53 protein and phosphorylates human p53 on serine 392 in vitro. Oncogene. 1999, 18 (17): 2690-2702. 10.1038\/sj.onc.1202620.","journal-title":"Oncogene"},{"issue":"5","key":"340_CR30","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1016\/0092-8674(92)90562-Q","volume":"71","author":"TR Hupp","year":"1992","unstructured":"Hupp TR, Meek DW, Midgley CA, Lane DP: Regulation of the specific DNA binding function of p53. Cell. 1992, 71 (5): 875-886. 10.1016\/0092-8674(92)90562-Q.","journal-title":"Cell"},{"issue":"10","key":"340_CR31","doi-asserted-by":"crossref","first-page":"3253","DOI":"10.1002\/j.1460-2075.1990.tb07524.x","volume":"9","author":"DW Meek","year":"1990","unstructured":"Meek DW, Simon S, Kikkawa U, Eckhart W: The p53 tumour suppressor protein is phosphorylated at serine 389 by casein kinase II. Embo J. 1990, 9 (10): 3253-3260.","journal-title":"Embo J"},{"key":"340_CR32","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/1756-8722-6-23","volume":"6","author":"MN Saha","year":"2013","unstructured":"Saha MN, Qiu L, Chang H: Targeting p53 by small molecules in hematological malignancies. J Hematol Oncol. 2013, 6: 23-10.1186\/1756-8722-6-23.","journal-title":"J Hematol Oncol"}],"container-title":["Journal of Hematology &amp; Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1756-8722-6-71.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T01:30:26Z","timestamp":1630546226000},"score":1,"resource":{"primary":{"URL":"https:\/\/jhoonline.biomedcentral.com\/articles\/10.1186\/1756-8722-6-71"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,9,20]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["340"],"URL":"https:\/\/doi.org\/10.1186\/1756-8722-6-71","relation":{},"ISSN":["1756-8722"],"issn-type":[{"value":"1756-8722","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,9,20]]},"assertion":[{"value":"22 August 2013","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 September 2013","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 September 2013","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"71"}}