TY - JOUR
T1 - Organ-specific susceptibility of p53 knockout mice to N-bis(2-hydroxypropyl)nitrosamine carcinogenesis
AU - Hirata, Akihiro
AU - Tsukamoto, Tetsuya
AU - Yamamoto, Masami
AU - Sakai, Hiroki
AU - Yanai, Tokuma
AU - Masegi, Toshiaki
AU - Donehower, Lawrence A.
AU - Tatematsu, Masae
N1 - Funding Information:
We thank Ms Naoko Ban and Ms Saori Kobayashi for their expert technical assistance and Dr Malcolm A. Moore for revision of the scientific English language. This work was supported in part by Grants-in-Aid from the Ministry of Health, Labour and Welfare and the Ministry of Education, Culture, Sports, Science and Technology of Japan.
PY - 2006/7/18
Y1 - 2006/7/18
N2 - 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.
AB - 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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U2 - 10.1016/j.canlet.2005.07.022
DO - 10.1016/j.canlet.2005.07.022
M3 - Article
C2 - 16150539
AN - SCOPUS:33744981825
SN - 0304-3835
VL - 238
SP - 271
EP - 283
JO - Cancer Letters
JF - Cancer Letters
IS - 2
ER -
