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 – Mouse Genome Informatics
10465341 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
C57BL/6 Liver adenoma
  • dimethyl sulfoxide (DMSO)
Liver

0

C57BL/6 Liver adenoma
  • dimethylnitrosamine (DMN)
Liver

33.33 - 76.47

C57BL/6 Liver adenoma
  • 6-nitrochrysene (6-NC)
Liver

83.33 - 88.89

C57BL/6 Liver adenoma
  • 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)
Liver

5.56 - 7.14

B6.129S7-Trp53tm1Brd/+ Liver adenoma
  • dimethyl sulfoxide (DMSO)
Liver

0

B6.129S7-Trp53tm1Brd/+ Liver adenoma
  • dimethylnitrosamine (DMN)
Liver

0 - 1.14

B6.129S7-Trp53tm1Brd/+ Liver adenoma
  • 6-nitrochrysene (6-NC)
Liver

0 - 20

B6.129S7-Trp53tm1Brd/+ Liver adenoma
  • 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)
Liver

5.88 - 13.33