Published in:
01-06-2003 | Original Paper
High susceptibility of nullizygous p53 knockout mice to colorectal tumor induction by 1,2-dimethylhydrazine
Published in: Journal of Cancer Research and Clinical Oncology | Issue 6/2003
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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.