Reference - Detail
RRC ID | 6005 |
---|---|
Author | Sakai H, Tsukamoto T, Yamamoto M, Shirai N, Iidaka T, Hirata A, Yanai T, Masegi T, Donehower LA, Tatematsu M. |
Title | High susceptibility of nullizygous p53 knockout mice to colorectal tumor induction by 1,2-dimethylhydrazine. |
Journal | J Cancer Res Clin Oncol |
Abstract |
PURPOSE:The susceptibility of male p53 nullizygote (-/-), heterozygote (+/-), and wild-type (+/+) mice to 1,2-dimethylhydrazine (DMH) induction of colon carcinogenesis was investigated. METHODS:In a preliminary short-term experiment, male mice of three genotypes were given s.c. of 20 mg/kg DMH once weekly for 5 weeks. In a medium-term experiment, mice were given weekly s.c. of DMH for 15 weeks. In a long-term experiment, male p53 (+/-) and (+/+) mice were given weekly injections of DMH for 15 weeks, and killed at week 30. RESULTS:In the medium-term experiment, carcinomas were observed in 70% of p53 (-/-) mice, although there were no carcinomas in p53 (+/+) and (+/-) mice. In the long-term experiment, there was no significant difference in incidences of adenomas and carcinomas between p53 (+/+) and (+/-) mice. PCR-single strand conformation polymorphism analysis of exons 5-8 of p53 gene revealed four mutations in one focal atypia, one adenoma, and two carcinomas, out of 56 colonic proliferative lesions in the medium- and long-term experiments. CONCLUSIONS:These results suggest that p53 might not be a direct target of DMH but complete loss of p53 might elevate susceptibility to DMH-induced colorectal carcinogenesis. |
Volume | 129(6) |
Pages | 335-40 |
Published | 2003-6-1 |
DOI | 10.1007/s00432-003-0443-9 |
PMID | 12743811 |
MeSH | 1,2-Dimethylhydrazine / adverse effects* Animals Carcinogens / adverse effects* Carcinoma / chemically induced* Carcinoma / genetics* Carcinoma / veterinary Cell Transformation, Neoplastic Colorectal Neoplasms / chemically induced* Colorectal Neoplasms / genetics* Colorectal Neoplasms / veterinary Disease Models, Animal Genes, p53 / genetics* Genotype Injections, Subcutaneous Male Mice Mice, Knockout |
IF | 3.656 |
Times Cited | 9 |
WOS Category | ONCOLOGY |
Resource | |
Mice | RBRC00159 |