22. Cytogenetic and Cellular Events during Radiation-induced Thymic Lymphomagenesis in p53 Heterozygous(+/-) B10 Mice
Kaoru Tanaka, Shiro Aizawa, Keiko Watanabe, Hideo Tsuji, Masahiro Mori, Hitoko Kamisaku, Yoko Hirabayashi, and Tohru Inoue
Keywords: thymic lymphomas, p53 heterozygous mice
Cellular and cytogenetic events in radiation-induced thymic lymphomagenesis were investigated in p53 heterozygous (+/-) mice following a single dose of whole-body irradiation. p53 heterozygous mice developed thymic lymphomas in a dose-dependent manner. The loss of wild type p53 allele (loss of heterozygosity; LOH) occurred in all/most thymic lymphomas induced in irradiated p53 heterozygous mice. Cytogenetic analysis for the mechanism of LOH indicated that the loss of wild type p53 gene in the lymphomas was caused by the duplication of the disrupted p53 gene allele through either homologous recombination or non-disjunctional chromosome duplication. The suppression of lymphoma development by the injection of normal bone marrow cells into mice after irradiation suggested that a critical event for the development of prelymphoma cells occurred between 4 and 5 weeks after irradiation. The results suggested that the loss of wild type p53 gene in thymocytes of p53 heterozygous mice preceded the development of prelymphoma cells after irradiation and may be a valuable marker for understanding of the role of radiation in radiation-induced leukemogenesis.
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