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
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 3.332
Times Cited 7
Mice C57BL/6-TgH(p53)-TgN(gpt)