Reference SummaryDass SB, Cancer Lett 1999 Aug 23;143(1):81-5
Title |
Evaluation of the transgenic p53+/- mouse for detecting genotoxic liver carcinogens in a short-term bioassay. | ||||
Authors |
Dass SB; Bucci TJ; Heflich RH; Casciano DA | ||||
Journal |
Cancer Lett | ||||
Volume |
143 | ||||
Issue |
1 | ||||
Year |
1999 | ||||
Pages |
81-5 | ||||
Abstract |
The transgenic p53-deficient heterozygous (p53+/-) mouse is prone to both spontaneous and induced tumors and has been proposed for use in a sensitive, short-term (6 months) assay for identifying genotoxic, multispecies carcinogens. It is not clear, however, if a short-term assay with p53+/- mice detects agents that target certain organs, in particular, the liver. In this study, we treated neonatal male p53+/- and p53+/+ mice with the genotoxic carcinogens dimethylnitrosamine (DMN), 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP), and 6-nitrochrysene (6-NC). In keeping with the methodology of the proposed short-term assay, the p53+/- mice were evaluated for tumors 7 months after treatment. Wild-type neonatal mice treated with genotoxic carcinogens are known to develop tumors within 1 year; hence, the p53+/+ animals used as controls were subjected to pathological examination at 1 year of age. Our results showed that PhIP was not tumorigenic in either group of mice. Liver tumor incidence increased significantly in the p53+/+ mice treated with DMN and 6-NC, indicating that the conditions of the bioassay were conducive to the promotion of liver tumorigenesis. On the other hand, these two chemicals failed to induce a significant increase in liver tumors in the p53+/- mice by seven months. This result suggests that a deficiency in the amount of p53 protein does not lead to accelerated liver tumorigenesis in mice, and contrasts with previous reports that show a decreased latency of tumors in non-liver targets. | ||||
Links |
J:57142 – MGI References 10465341 – National Library of Medicine/PubMed |
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Strain Notes
|
Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
---|---|---|---|---|---|
C57BL/6 | Liver adenoma | Liver |
0 |
||
C57BL/6 | Liver adenoma |
|
Liver |
33.3 - 76.5 |
|
C57BL/6 | Liver adenoma |
|
Liver |
83.3 - 88.9 |
|
C57BL/6 | Liver adenoma |
|
Liver |
5.6 - 7.1 |
|
B6.129S7-Trp53tm1Brd/+ | Liver adenoma | Liver |
0 |
||
B6.129S7-Trp53tm1Brd/+ | Liver adenoma |
|
Liver |
0 - 1.1 |
|
B6.129S7-Trp53tm1Brd/+ | Liver adenoma |
|
Liver |
0 - 20 |
|
B6.129S7-Trp53tm1Brd/+ | Liver adenoma |
|
Liver |
5.9 - 13.3 |