Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Radiation-associated loss of heterozygosity at the Ikaros locus on chromosome 11 in murine thymic lymphomas

Y Shimada PhD 1, M Nishimura 2, S Kakinuma PhD 3, M Okumoto PhD 4, S Wakana PhD 5

1,2,3 National Institute of Radiological Sciences, Chiba, Japan, 4 Research Institute of Advanced Science and Technology, Osaka Prefecture University, Osaka, Japan, 5 Central Institute for Experimental Animals, Kanagawa, Japan,

AIM: Although information on the molecular pathways in radiation carcinogenesis is being increasingly accumulated, the data are still relatively scanty. In order to find the tumor suppressor locus associated with radiation carcinogenesis, we determined the frequency and distribution of loss of heterozygosity (LOH) of X-ray-induced thymic lymphomas of B6C3F1, and compared the results with those for spontaneous lymphomas and N-ethylnitrosourea (ENU)-induced lymphomas. METHODS: Thymic lymphomas were induced in B6C3F1 mice by weekly exposure to 1.6 Gy whole body X-irradiation or administration with ENU (400ppm) in drinking water. RESULTS: We identified a unique locus with frequent LOH in the centromeric region of chromosome 11 of X-ray-induced lymphomas. This locus has never been observed to be altered similarly in either ENU-induced or spontaneously developed lymphomas, suggesting radiation specific molecular alteration. Linkage analysis revealed that the markers of the common LOH region were genetically linked to Ikaros, a master gene of lymphopoiesis. CONCLUSION: Although the presence of radiation-associated LOH in other loci cannot be ruled out, these results suggest a novel molecular pathway in induction of thymic lymphomas by ionizing radiation.

KEY WORDS: thymic lymphomas, Ikaros, radiation.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on genetic instability.