{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T09:10:01Z","timestamp":1761988201177},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,2,5]],"date-time":"2009-02-05T00:00:00Z","timestamp":1233792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2009,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Isocyanates (R\uf8ffN\uf8feC\uf8feO), one of the highly reactive industrial intermediates, possess the capability to modulate the bio\u2010molecules by forming toxic metabolites and adducts which may cause adverse health effects. Some of their toxic degradations have previously been unknown and overlooked; of which, molecular repercussions underlying their genetic hazards upon occupational\/accidental exposures still remain as an intricate issue and are hitherto unknown. To assess the genotoxic potential of methyl isocyanate in cultured mammalian cells after in vitro exposure, we performed a study in three different normal cell lines MM55.K (mouse kidney epithelial), B\/CMBA.Ov (mouse ovarian epithelial), and NIH\/3T3 (primary mouse embryonic fibroblast). Cellular DNA damage response was studied for qualitative phosphorylation states of ATM, \u03b3H2AX proteins and quantitative state of p53 phosphorylation; DNA cell cycle analysis and measure of cellular apoptotic index before and after treatment were also investigated. Our results demonstrate that methyl isocyanate by negatively regulating the DNA damage response pathway, might promote cell cycle arrest, and apoptosis in cultured mammalian cells suggestive of causing genetic alterations. We anticipate that these data along with other studies reported in the literature would help to design better approaches in risk assessment of occupational and accidental exposure to isocyanates. We also predict that increasing knowledge on DNA damage\u2010triggered signaling leading to cell death could provide new strategies for investigating the effects of DNA repair disorders and decreased repair capacity on the toxicity and carcinogenic properties of environmental toxins. Environ. Mol. Mutagen., 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/em.20469","type":"journal-article","created":{"date-parts":[[2009,2,7]],"date-time":"2009-02-07T04:05:12Z","timestamp":1233979512000},"page":"328-336","source":"Crossref","is-referenced-by-count":23,"title":["Analysis of cellular response to isocyanate using <i>N<\/i>\u2010succinimidyl <i>N<\/i>\u2010methylcarbamate exposure in cultured mammalian cells"],"prefix":"10.1002","volume":"50","author":[{"given":"Pradyumna Kumar","family":"Mishra","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Venkata Raghuram","family":"Gorantla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nabila","family":"Akhtar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priyanka","family":"Tamrakar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Subodh Kumar","family":"Jain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kewal Krishan","family":"Maudar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,4]]},"reference":[{"key":"e_1_2_1_2_1","first-page":"269","article-title":"Effects of methyl isocyanate on rat muscle cells in culture","volume":"45","author":"Anderson D","year":"1988","journal-title":"Br J Ind Med"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.2001.02225.x"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.06.023"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2007.02.009"},{"key":"e_1_2_1_6_1","doi-asserted-by":"crossref","first-page":"313","DOI":"10.3727\/096504005776404553","article-title":"The antineoplastic efficacy of the prodrug cloretazine is produced by the synergistic interaction of carbamoylating and alkylating products of its activation","volume":"15","author":"Baumann RP","year":"2005","journal-title":"Oncol Res"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx0600853"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/20014091111974"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204484"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1039\/b800850g"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90039-X"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.9951"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.6.9.4211"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90500-P"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2008.03.006"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1099-1263(199611)16:6<469::AID-JAT373>3.0.CO;2-Q"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1089\/dna.2006.25.406"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.2550130105"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.2.661-670.2005"},{"key":"e_1_2_1_20_1","first-page":"167","article-title":"Genotoxicity studies on mice after short term inhalation exposure to methyl isocyanate","volume":"59","author":"Kar RN","year":"1989","journal-title":"Cytobios"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2008.01.014"},{"key":"e_1_2_1_22_1","first-page":"305","article-title":"Gamma\u2010H2AX\u2014a novel biomarker for DNA double\u2010strand breaks","volume":"22","author":"Kuo LJ","year":"2008","journal-title":"In Vivo"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2004.03.029"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2006.11.015"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00344a017"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.21.16202"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.2860090104"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.187"},{"key":"e_1_2_1_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2004.03.027"},{"key":"e_1_2_1_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1218(92)90244-T"},{"key":"e_1_2_1_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.20260"},{"key":"e_1_2_1_32_1","unstructured":"MittraI SamantUC ModiGK MishraPK Bhuvaneshwar GS.2007. 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