High susceptibility of nullizygous p53 knockout mice to colorectal tumor induction by 1,2-dimethylhydrazine.

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.

• Authors: Hiroki Sakai, Tetsuya Tsukamoto, Masami Yamamoto, Norimitsu Shirai, Takeshi Iidaka, Akihiro Hirata, Tokuma Yanai, Toshiaki Masegi, Lawrence A Donehower, Masae Tatematsu
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 129 Issue 6 Pg. 335-40 (Jun 2003) ISSN: 0171-5216 [Print] Germany
• PMID: 12743811 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carcinogens
• 1,2-Dimethylhydrazine

Topics

• 1,2-Dimethylhydrazine (adverse effects)
• Animals
• Carcinogens (adverse effects)
• Carcinoma (chemically induced, genetics, veterinary)
• Cell Transformation, Neoplastic
• Colorectal Neoplasms (chemically induced, genetics, veterinary)
• Disease Models, Animal
• Genes, p53 (genetics)
• Genotype
• Injections, Subcutaneous
• Male
• Mice
• Mice, Knockout