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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2003-4-22
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pubmed:abstractText |
In human cancer, alterations in the p53 tumor suppressor gene are the most common genetic alterations. The aim of the present study was to detect sensitivity of the p53 (+/-) mice and their littermates p53 (+/+) mice to N, N-dibutylnitrosamine (DBN) carcinogenicity. In experiment 1, 6-7-week-old p53 (+/-) and p53 (+/+) mice were treated with 0, 0.025 and 0.05% DBN, respectively, in drinking water for 20 weeks. Esophageal squamous cell and urinary bladder transitional cell carcinomas (TCCs) and fibrosarcomas were found to be significantly increased in p53 (+/-) mice treated with doses of DBN compared to p53 (+/+) mice administered similar doses. In experiment 2, 6-7-week-old p53 (+/-) and p53 (+/+) mice were administered 0 or 0.05 % DBN in drinking water for 8 weeks. Immunohistochemical staining revealed a significant increase in numbers of p53 and bromodeoxyuridine (BrdU) positive cells in the esophageal and urinary bladder epithelia of DBN-treated p53 (+/-) mice compared to p53 (+/+) mice administered DBN. Molecular analysis revealed point mutations in the residual p53 allele in four of eight (50%) esophageal mucosa of DBN-treated p53 (+/-) mice, and in three of eight (38%) of treated p53 (+/+) mice. The results show that p53 (+/-) mice were sensitive to DBN treatment with respect to esophageal and bladder tumor development, with a mechanism that could be confined to early mutations of the residual p53 allele and increased cellular proliferation in the target organs.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0304-3835
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
8
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pubmed:volume |
194
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
45-54
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12706858-Alleles,
pubmed-meshheading:12706858-Animals,
pubmed-meshheading:12706858-Body Weight,
pubmed-meshheading:12706858-Bromodeoxyuridine,
pubmed-meshheading:12706858-Carcinogens,
pubmed-meshheading:12706858-Carcinoma, Squamous Cell,
pubmed-meshheading:12706858-Carcinoma, Transitional Cell,
pubmed-meshheading:12706858-Cell Division,
pubmed-meshheading:12706858-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:12706858-Cyclins,
pubmed-meshheading:12706858-Esophageal Neoplasms,
pubmed-meshheading:12706858-Genes, p53,
pubmed-meshheading:12706858-Genetic Predisposition to Disease,
pubmed-meshheading:12706858-Immunohistochemistry,
pubmed-meshheading:12706858-Male,
pubmed-meshheading:12706858-Mice,
pubmed-meshheading:12706858-Mice, Inbred C57BL,
pubmed-meshheading:12706858-Mice, Knockout,
pubmed-meshheading:12706858-Mice, Transgenic,
pubmed-meshheading:12706858-Mutation,
pubmed-meshheading:12706858-Nitrosamines,
pubmed-meshheading:12706858-Organ Size,
pubmed-meshheading:12706858-Point Mutation,
pubmed-meshheading:12706858-Polymerase Chain Reaction,
pubmed-meshheading:12706858-Polymorphism, Single-Stranded Conformational,
pubmed-meshheading:12706858-Sequence Analysis, DNA,
pubmed-meshheading:12706858-Time Factors,
pubmed-meshheading:12706858-Urinary Bladder Neoplasms
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pubmed:year |
2003
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pubmed:articleTitle |
High susceptibility of p53 knockout mice to esophageal and urinary bladder carcinogenesis induced by N, N-dibutylnitrosamine.
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pubmed:affiliation |
Department of Pathology, Osaka City University Medical School, 1-4-3, Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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