Tongue carcinogenic susceptibility of p53 deficient mice to methyl-n-amylnitrosamine

Norimitsu Shirai, Tetsuya Tsukamoto, Masami Yamamoto, Takeshi Iidaka, Hiroki Sakai, Tokuma Yanai, Toshiaki Masegi, Lawrence A. Donehower, Masae Tatematsu

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5 Citations (Scopus)

Abstract

Mutation of the p53 tumor suppressor gene is a common genetic alteration in human squamous cell carcinoma of the tongue. Mice deficient in p53 have recently attracted attention for their potential to identify chemical genotoxins. In this study we investigated the susceptibility of p53 nullizygous (-/-), heterozygous (+/-), and wild type (+/+) mice to methyl-n-amylnitrosamine (MNAN) induced squamous cell carcinoma (SCC) of the tongue. The p53 (+/-), and (+/+) mice were treated with 5 p.p.m. MNAN in drinking water for 8 weeks then held without further treatment for an additional 7 or 17 weeks, and killed at 15 or 25 experimental weeks. A separate group of the p53 (-/-) mice were given 5 p.p.m. MNAN for 8 weeks and were killed at 15 weeks. At 15 weeks, SCCs and papillomas were observed in 5/12 (41.7%) and 2/12 (16.7%) of p53 (-/-) mice, respectively, but not in p53 (+/-) and (+/+) mice. At 25 weeks, carcinomas in situ (CIS) were detected in 1/16 (6.3%) of p53 (+/-) and 1/13 (7.7%) of p53 (+/+) mice, and a papilloma was observed in the p53 (+/-) mouse which had CIS. PCR-single strand conformation polymorphism analysis of exons 5-8 of the p53 gene demonstrated a missense mutation in the CIS from p53 (+/+) mouse. These results suggest that a lack of p53 gene function predisposes the tongue to the development of SCCs in mice treated with MNAN, and show that p53 (-/-) mouse was a useful model for demonstrating carcinogenicity of MNAN to tongue.

Original languageEnglish
Pages (from-to)209-214
Number of pages6
JournalJournal of Toxicologic Pathology
Volume15
Issue number4
DOIs
Publication statusPublished - 2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Toxicology

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    Shirai, N., Tsukamoto, T., Yamamoto, M., Iidaka, T., Sakai, H., Yanai, T., Masegi, T., Donehower, L. A., & Tatematsu, M. (2002). Tongue carcinogenic susceptibility of p53 deficient mice to methyl-n-amylnitrosamine. Journal of Toxicologic Pathology, 15(4), 209-214. https://doi.org/10.1293/tox.15.209