{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T20:37:48Z","timestamp":1762979868815,"version":"build-2065373602"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2011,12,19]],"date-time":"2011-12-19T00:00:00Z","timestamp":1324252800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>To evaluate the impact of p27 on carcinogenesis in various organs, <jats:italic>N<\/jats:italic>\u2010methyl\u2010<jats:italic>N<\/jats:italic>\u2010nitrosourea (MNU), a direct\u2010acting alkylating agent, was given to p27 knock\u2010out mice. Groups of 20\u201340 male and female mice with null, hetero\u2010 or wild\u2010type p27 alleles were given drinking water containing 240\u2009ppm MNU or distilled water every other week for five cycles. The incidence and multiplicity of the induced proliferative lesions were then histologically evaluated at weeks 14 and 20. MNU treatment induced various lesions including squamous hyperplasia and squamous cell carcinoma in the forestomach, atypical hyperplasia and adenocarcinomas in the fundic and pyloric glands, adenomas and adenocarcinomas in the duodenum, malignant lymphomas in the thymus, liver, kidney and spleen and alveolar hyperplasia, adenomas, adenocarcinomas and malignant lymphomas in the lung. Although the incidences of the lesions in the forestomach, fundic and pyloric glands did not differ among the p27 genotypes, those of alveolar hyperplasia of the lung and malignant lymphoma of the thymus were significantly increased in p27\u2010null males as compared with both wild\u2010 and hetero\u2010type animals. Moreover, in both p27<jats:sup>+\/+<\/jats:sup> and p27<jats:sup>+\/\u2212<\/jats:sup> cases, the rates for p27\u2010positive cells were obviously increased in proliferative lesions of the pyloric gland and the lung. However, an increased rate of p27\u2010positive cells was not observed in malignant lymphoma of the thymus. These findings suggest that p27 does not control the cell cycle equally in all organs affected by MNU\u2010induced carcinogenesis. Copyright \u00a9 2011 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.1770","type":"journal-article","created":{"date-parts":[[2011,12,19]],"date-time":"2011-12-19T10:04:41Z","timestamp":1324289081000},"page":"471-479","source":"Crossref","is-referenced-by-count":4,"title":["Organ differences in the impact of p27<sup>kip1<\/sup> deficiency on carcinogenesis induced by <b><i>N<\/i>\u2010methyl\u2010<i>N<\/i>\u2010nitrosourea<\/b>"],"prefix":"10.1002","volume":"33","author":[{"given":"Kumiko","family":"Ogawa","sequence":"first","affiliation":[{"name":"Department of Experimental Pathology and Tumor Biology Nagoya City University Graduate School of Medical Sciences  1 Kawasumi, Mizuho\u2010cho, Mizuho\u2010ku Nagoya 467\u20108601 Japan"},{"name":"Division of Pathology National Institute of Health Sciences  1\u201018\u20101 Kamiyoga, Setagaya\u2010Ku Tokyo 158\u20108501 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiya","family":"Murasaki","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology and Tumor Biology Nagoya City University Graduate School of Medical Sciences  1 Kawasumi, Mizuho\u2010cho, Mizuho\u2010ku Nagoya 467\u20108601 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Sugiura","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology and Tumor Biology Nagoya City University Graduate School of Medical Sciences  1 Kawasumi, Mizuho\u2010cho, Mizuho\u2010ku Nagoya 467\u20108601 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cell Biology Nagoya City University Graduate School of Medical Sciences  1 Kawasumi, Mizuho\u2010cho, Mizuho\u2010ku Nagoya 467\u20108601 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoyuki","family":"Shirai","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology and Tumor Biology Nagoya City University Graduate School of Medical Sciences  1 Kawasumi, Mizuho\u2010cho, Mizuho\u2010ku Nagoya 467\u20108601 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,12,19]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0297-227"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001911"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/90.12.916"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/09553008514552591"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/24179"},{"key":"e_1_2_6_7_1","first-page":"1","volume-title":"Proliferative Lesions of the Non\u2010glandular and Glandular Stomach in Rats. 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