{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T04:01:49Z","timestamp":1777003309717,"version":"3.51.4"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2018,12,2]],"date-time":"2018-12-02T00:00:00Z","timestamp":1543708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Defense for Health Affairs","award":["CA140822"],"award-info":[{"award-number":["CA140822"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Kidneys are one of the main dose-limiting organs in radiotherapeutic procedures of lower abdomen. Likewise, the threat of exposure of radiosensitive organs such as kidneys in warfare or radiation accidents among military personal or due to terrorist activities in general public is of increasing concern. These events warrant the need for appropriate animal models to study the acute and chronic effects of low- and high-dose rate radiation exposures. In this study, for the first time, we validated Tsc2+\/\u2013 mouse model to study whether radiation accelerates carcinogenesis in kidneys. Tsc2+\/\u2013 mice at increasing age groups at 8 and 10 months were exposed to repeated doses of gamma radiation (0.4 Gy \u00d7 5) and assessed for aggravated kidney tumor formation at 2 months post-irradiation. Animals from irradiated group showed a significant increase in numbers of bilateral, multifocal tumors compared with mock-irradiated animals. Intra-glomerular reactive oxygen species (ROS) levels measured by dihydroethidium florescence showed significant increases in ROS production in irradiated Tsc2+\/\u2013 mice compared with non-irradiated animals. Similarly, selective hematological parameters and glomerular filtration rate were further reduced significantly in irradiated Tsc2+\/\u2013 mice. Tsc2 protein, tuberin in irradiated mice, however, remains at the same reduced levels as that of the mock-irradiated heterozygous Tsc2 mice. The results indicate that radiation alters kidney homeostatic function and influences high spontaneous incidence of renal cell carcinoma in this rodent model. Repurposing of Tsc2+\/\u2013 mice model will, therefore, provide a unique opportunity to study acute and delayed effects of radiation in the development of kidney cancers.<\/jats:p>","DOI":"10.1093\/carcin\/bgy172","type":"journal-article","created":{"date-parts":[[2018,11,29]],"date-time":"2018-11-29T23:17:07Z","timestamp":1543533427000},"page":"782-790","source":"Crossref","is-referenced-by-count":3,"title":["Heterozygous Tsc2 (Tsc2+\/\u2013) mouse model to study induced renal cancer in response to ionizing radiation at low doses"],"prefix":"10.1093","volume":"40","author":[{"given":"Sureshkumar","family":"M A","sequence":"first","affiliation":[{"name":"Department of Pathology, School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0868-7444","authenticated-orcid":false,"given":"Caroline R","family":"Delma","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krishnan","family":"Manickam","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumathy","family":"Mohan","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samy L","family":"Habib","sequence":"additional","affiliation":[{"name":"Department of Cell System and Anatomy, School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohan","family":"Natarajan","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,12,2]]},"reference":[{"key":"2019070605525033600_CIT0001","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21442","article-title":"Cancer statistics, 2018","volume":"68","author":"Siegel","year":"2018","journal-title":"CA. 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Phys.,"}],"container-title":["Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/carcin\/article-pdf\/40\/6\/782\/28911752\/bgy172.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,7,6]],"date-time":"2019-07-06T05:53:05Z","timestamp":1562392385000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/carcin\/article\/40\/6\/782\/5225569"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,2]]},"references-count":48,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2018,12,2]]},"published-print":{"date-parts":[[2019,7,6]]}},"URL":"https:\/\/doi.org\/10.1093\/carcin\/bgy172","relation":{},"ISSN":["0143-3334","1460-2180"],"issn-type":[{"value":"0143-3334","type":"print"},{"value":"1460-2180","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,6]]},"published":{"date-parts":[[2018,12,2]]}}}