Early detection of p53-/- thymocytes appeared during radiation-induced thymic lymphomagenesis in p53 heterozygous (+/-) B10 mice
| Autor: | Aizawa, Shirou, Tanaka, Kaoru, Mori, Masahiko, Yoshida, Kazuko |
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| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Popis: | Radiation exposure is know to be highly leukemmogenic, but the mechanism action is not yet understood. Studies with the p53 heterozygous mouse have shown that a single dose of radiation can induce a high incidence of thymic lymphomas, most of which manifest the loss of wild-type p53 allele. The loss of heterozygosity (LOH) in the p53 gene is thus thought to be an early event in radiation-induced thymic lymphomagenesis. Thus, the p53 heterozygous mice might be a useful model for the study of consequences of radiation-exposure. However, sensitive detection of p53-/- thymocytes appeared in p53+/- thymocyte population was needed to examine appearance of p53-/- thymocyte in p53 heterozygous (+/-) B10 mice in the early stage of radiation-induced thymic lymphomagenesis. In this study, we characterized highly radioresistant thymocytes as a candidate of p53-/- thymocytes, because the enrichment of p53-/- thymocyte by a high dose of irradiation could be expected from the facts that p53+/- thymocytes are sensitive to radiation-induced apoptosis but p53-/- thymocytes highly resistant. At various times post irradiation (6Gy) as lymphoma-inducing treatment, p53 heterozygous B10 mice were treated with a high dose (30Gy)of whole-body irradiation to enrich p53-/- thymocytes and, 24 hours later, the remaining thymocytes were assayed for surface marker and p53 genotype. In a significant fraction of the mice 7wks after 6Gy-irradiation, we observe an abnormal increase of relative cell number of CD4+CD8+ thymocytes remaining in the thymus of highly irradiated mice and such abnormal thymocytes could be detected even 5 weeks after the irradiation. The abnormal CD4+CD8+ thymocytes werer shown by PCR analysis of sorted cells to contain cells ith p53-/- genotype. The data obtained so far suggest that p53-/- thymocytes may appear as prelymphoma cells within several weeks post irradiation in CD4+CD8+ thymocyte population of irradiated p53 heterozygous mice. 第１２回国際放射線研究会議 |
| Databáze: | OpenAIRE |
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