Organ-specific susceptibility of p53 knockout mice to N-bis(2-hydroxypropyl)nitrosamine carcinogenesis.
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.
Hirata
Akihiro
A
Division of Oncological Pathology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
Tsukamoto
Tetsuya
T
Yamamoto
Masami
M
Sakai
Hiroki
H
Yanai
Tokuma
T
Masegi
Toshiaki
T
Donehower
Lawrence A
LA
Tatematsu
Masae
M
D000818:Animals; D005260:Female; D016158:Genes, p53; D006391:Hemangioma / Q000139:chemically induced; D006394:Hemangiosarcoma / Q000139:chemically induced; D008113:Liver Neoplasms / Q000139:chemically induced; D008175:Lung Neoplasms / Q000139:chemically induced; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D009602:Nitrosamines / Q000633:toxicity*; D009928:Organ Specificity; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D009602:Nitrosamines; D016159:Tumor Suppressor Protein p53; C012457:diisopropanolnitrosamine