Proj
J-GLOBAL ID:200904061775026284  Research Project code:9911002488 Update date:Mar. 30, 2001

Molecular and cellular mechanisms of radiation-induced thymic lymphomagenesis

放射線誘発リンパ腫の発生機構の分子生物学的研究
Study period:1999 - 2000
Organization (1):
Investigating Researcher (4):
Research overview:
Since the T cell receptor rearangement is a sequential process and unique to the progeny of each clone, we investigated the early initiating events in radiation-induced thymic lymphomagenesis by comparing the oncogenic alterations with the pattern of gamma T cell receptor (TCR) rearrangements. The results indicated that in half of the irradiated mice, chromosome aberrations or translocations such as trisomy 15, t(7F; 10C), t(1A; 13D) or t(6A; XB) occuring in single progenitor cells at early T cell differentiation either just before or after gamma TCR rearrangements, might be important candidates for initiating events. In the other half of the irradiated mice, microgenetic changes were suggested to be initial events and also might take place in single progenitor cells just before or right after gamma TCR rearrangements. To further investigate these genetic alterations in radiation-induced lymphomagenesis, we employed the following two approaches: the cDNA subtraction method and the isolation of the cancer-relatedgenes monoclonal antibody. We established an improved cDNA subtraction method employing biotin-conjugated primers and efficient cDNA selection, and we isolated the lymphoma specific cDNA clones using it. From the screening of 1750 clones by dot blot hybridization, 220 lymphoma-specific cDNA clones were obtained. Some of these clones also expressed in other groups of lymphomas. Moreover, these clones expressed in the thymus of mice 14 and 26 days after X-irradiation (1.61 Gy X 4) but not in the thymus of non-irradiated mice. These results indicated that the expression of these genes induced by lymphomagenic X-irradiation lasted until the onset of lymphomas. Genomic instability might be induced by the abnormal expression of specific genes among these genes.
Keywords (6):
radiation-induced thymic lymphomagenesis ,  T cell receptor rearrangement ,  chromosome aberrations ,  cDNA subtraction method ,  radiation-induced genomic instability ,  T cell differentiation
Research program: Ordinary Research
Ministry with control over the research :
Ministry of Education, Culture, Sports, Science and Technology
Organization with control over the research:
National Institutes for Quantum and Radiological Science and Technology
Research budget: 1999: \1,200,000

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