Organ-specific susceptibility of p53 knockout mice to N-bis(2-hydroxypropyl)nitrosamine carcinogenesis |
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Authors: | Hirata Akihiro Tsukamoto Tetsuya Yamamoto Masami Sakai Hiroki Yanai Tokuma Masegi Toshiaki Donehower Lawrence A Tatematsu Masae |
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Affiliation: | Division of Oncological Pathology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan. |
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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. |
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