Reference SummaryFinnberg N, Cancer Lett 2004 Apr 30;207(2):149-55

Title

Heterozygous p53-deficient (+/-) mice develop fewer p53-negative preneoplastic focal liver lesions in response to treatment with diethylnitrosamine than do wild-type (+/+) mice.

Authors

Finnberg N; Stenius U; Hogberg J

Journal

Cancer Lett

Volume

207

Issue

2

Year

2004

Pages

149-55

Abstract

In the present study p53+/- and p53+/+C57BL/6 female mice were administered diethylnitrosamine (DEN) once each week for 15-20 weeks. After sacrifice we analyzed the number and size of preneoplastic liver lesions, and found that the same numbers of lesions of similar sizes developed in the two genotypes of mice. We also distinguished between two phenotypes: 'p53-positive' and 'p53-negative' lesions (i.e. lesions with or without a p53 response to DNA damage, as assessed by immunohistochemical staining for p53 24 h after administration of a challenging dose of DEN). In wild-type mice we found the same proportion of p53-positive and p53-negative lesions as in rats, i.e. about 75% of the lesions were p53-negative. However, the number and the percentage of p53-negative lesions were lower in +/- mice (17%, P < 0.05). These results were confirmed by Western blot analysis revealing a clear p53 response in lesions only in the case of +/- mice. These findings support our previous conclusion that an attenuated p53 response in preneoplastic lesions compared to normal tissue may give these lesions a growth advantage under conditions of subchronic genotoxic stress. Furthermore, our findings suggest that the presence of only one functional p53 allele in p53+/- mice is sufficient to counteract the growth advantage that such an attenuated p53 response appears to confer.

Links

J:89140 – MGI References
15072823 – National Library of Medicine/PubMed

Strain Notes

Strain Note
B6.129S7-Trp53tm1Brd/+ Mice were purchased from Taconic and were at backcross generation N12.

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
B6.129S7-Trp53tm1Brd/+ Liver preneoplastic lesion
  • diethylnitrosamine (DEN)
Liver

observed

C57BL/6 Liver preneoplastic lesion
  • diethylnitrosamine (DEN)
Liver

observed