Organ-specific susceptibility of p53 knockout mice to N-bis(2-hydroxypropyl)nitrosamine carcinogenesis.

Abstract

To elucidate which is the major determinant of susceptibility of p53 deficient mice, the carcinogen or the target organ, N-bis(2-hydroxypropyl)nitrosamine was administered to induce tumors in multi-organs. In a 15-week experiment, the incidences of both lung and hepatic vascular tumors were found to be significantly higher in p53 nullizygous (-/-) than in heterozygous (+/-) and wild-type (+/+) mice, indicating universal susceptibility of p53 (-/-) mice. In a 40-week experiment, p53 (+/-) mice showed increased susceptibility only with regard to vascular tumors, coinciding with significantly more frequent (60%) p53 gene mutations, in comparison with lung tumors with their low mutation rate (10.8%) (P<0.005). These results indicate that the target organ may be a more important factor than the carcinogen in determining susceptibility of p53 (+/-) mice.

• Authors: Akihiro Hirata, Tetsuya Tsukamoto, Masami Yamamoto, Hiroki Sakai, Tokuma Yanai, Toshiaki Masegi, Lawrence A Donehower, Masae Tatematsu
• Journal: Cancer letters (Cancer Lett) Vol. 238 Issue 2 Pg. 271-83 (Jul 18 2006) ISSN: 0304-3835 [Print] Ireland
• PMID: 16150539 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nitrosamines
• Tumor Suppressor Protein p53
• diisopropanolnitrosamine

Topics

• Animals
• Female
• Genes, p53
• Hemangioma (chemically induced)
• Hemangiosarcoma (chemically induced)
• Liver Neoplasms (chemically induced)
• Lung Neoplasms (chemically induced)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mutation
• Nitrosamines (toxicity)
• Organ Specificity
• Tumor Suppressor Protein p53 (physiology)