Abstract
Since the T cell receptor rearrangement 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 γ T cell receptor (TCR) rearrangements. We reported previously that after leukemogenic irradiation, preneoplastic cells developed, albeit infrequently, from thymic leukemia antigen‐2+ (TL‐2+) thymocytes. Limited numbers of TL‐2+ cells from individual irradiated B10.Thy 1.1 mice were injected into B10.Thy 1.2 mice intrathymically, and the common genetic changes among the donor‐type T cell lymphomas were investigated with regard to p53 gene and chromosome aberrations. The results indicated that some mutations in the p53 gene had taken place in these lymphomas, hut there was no common mutation among the donor‐type lymphomas from individual irradiated mice, suggesting that these mutations were late‐occurring events in the process of oncogenesis. On the other hand, there were common chromosome aberrations or translocations such as trisomy 15, t(7F;10C), t(1A;13D) or t(6A;XB) among the donor‐type lymphomas derived from half of the individual irradiated mice. This indicated that the aberrations/translocations, which occurred in single progenitor cells at the early T cell differentiation either just before or after γ T cell receptor rearrangements, might he important candidates for initiating events. In the donor‐type lymphomas from the other half of the individual irradiated mice, microgenetic changes were suggested to be initial events and also might take place in single progenitor cells just before or right after γ TCR rearrangements.
Keywords: Initiation, p53, Chromosome aberration, T cell receptor rearrangement, Clonality
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REFERENCES
- 1. ) Kaplan , H. S. and Brown , M. B.A quantitative dose‐response study of lymphoid tumor development in irradiated C57 black mice . J. Natl. Cancer Inst. 13 , 185 – 208 ( 1952. ). [PubMed] [Google Scholar]
- 2. ) Muto , M. , Kubo , E. and Sado , T.Cellular events during radiation‐induced thymic leukemogenesis in mice: abnormal T cell differentiation in the thymus and defect of thymocyte precursors in the bone marrow after split‐dose irradiation . J. Immunol. 134 , 2026 – 2031 ( 1985. ). [PubMed] [Google Scholar]
- 3. ) Muto , M. , Sado , T. , Hayata , I. , Nagasawa , F. , Kamisaku , H. and Kubo , E.Reconfirmation of indirect induction of radiogenic lymphomas using thymectomized, irradiated B10 mice grafted with neonatal thymuses from Thy 1 congenic donors . Cancer Res. 43 , 3822 – 3827 ( 1983. ). [PubMed] [Google Scholar]
- 4. ) Defresne , M. P. , Rongy , A. M. , Greimers , R. and Boniver , J.Cellular aspects of radiation leukemogenesis in C57BL/Ka mice: alterations to thymic microenvironment and lymphopoiesis . Leuk. Res. 10 , 783 – 789 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 5. ) Boniver , J. , Decleve , A. , Lieberman , M. , Honsik , C. , Travis , M. and Kaplan , H. S.Marrow‐thymus interactions during radiation leukemogenesis in C57BL/Ka mice . Cancer Res. 41 , 390 – 392 ( 1981. ). [PubMed] [Google Scholar]
- 6. ) Sen‐Majumdar , A. , Guidos , C. , Kina , T. , Lieberman , M. and Weissman , I. L.Characterization of preneoplastic thymocytes and of their neoplastic progression in irradiated C57BL/Ka mice . J. Immunol. 153 , 1581 – 1592 ( 1994. ). [PubMed] [Google Scholar]
- 7. ) Muto , M. , Kubo , E. and Sado , T.Development of prelymphoma cells committed to thymic lymphomas during radiation‐induced thymic lymphomagenesis in B10 mice . Cancer Res. 47 , 3469 – 3472 ( 1987. ). [PubMed] [Google Scholar]
- 8. ) Muto , M. , Kubo , E. , Kamisaku , H. and Sado , T.Phenotypic characterization of thymic prelymphoma cells of B10 mice treated with split‐dose irradiation . J. Immunol. 144 , 849 – 853 ( 1990. ). [PubMed] [Google Scholar]
- 9. ) Cowell , J. K.A photographic representation of the variability in the G‐banded structure of the chromosomes in the mouse karyotype . Chromosome 89 , 294 – 320 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 10. ) Committee on Standard Genetic Nomenclature for Mice , Standard karyotype of the mouse.Mus musculus . J. Hered. , 63 , 69 ( 1972. ). [PubMed] [Google Scholar]
- 11. ) Maniatis , T. , Fritsch , E. F. and Sambrook , J.In “ Molecular Cloning. A Laboratory Manual ,” pp. 324 – 389 ( 1982. ). Cold Spring Harbor Laboratory Press; , New York . [Google Scholar]
- 12. ) Kubo , E. , Muto , M. , Sado , T. , Takeshita , S. , Shimizu , T. and Yamagishi , H.Novel TCR gene rearrangements and expression in radiation‐induced thymic lymphomas . J. Radiat. Res. 33 , 227 – 242 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 13. ) Shimizu , T. , Muto , M. , Kubo , E. , Sado , T. and Yamagishi , H.Multiple pre‐neoplastic events and clonal selection of radiation induced mouse thymic lymphomas shown by TCR gene rearrangements . Leuk. Res. 17 , 959 – 965 ( 1993. ). [DOI] [PubMed] [Google Scholar]
- 14. ) Zakut‐Houri , R. , Oren , M. , Bienz , B. , Lavie , V. , Hazum , S. and Givol , D.A single gene and a pseudogene for the cellular tumour antigen p53 . Nature 306 , 594 – 597 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 15. ) Brathwaite , O. , Bayona , W. and Newcomb , E. W.p53 mutations in C57BL/6J murine thymic lymphomas induced by γ‐irradiation and N‐methylnitrosourea . Cancer Res. 52 , 3791 – 3795 ( 1992. ). [PubMed] [Google Scholar]
- 16. ) Orita , M. , Suzuki , Y. , Sekiya , T. and Hayashi , K.Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction . Genomics 5 , 874 – 879 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 17. ) Sanger , F.Determination of nucleotide sequences in DNA . Science 214 , 1205 – 1210 ( 1981. ). [DOI] [PubMed] [Google Scholar]
- 18. ) Nenoi , M. , Mita , K. , Ichimura , S. and Cartwright , I. L.Novel structure of a Chinese hamster polyubiquitin gene . Biochim. Biophys. Acta 1204 , 271 – 278 ( 1994. ). [DOI] [PubMed] [Google Scholar]
- 19. ) Pardoll , D. M. , Fowlkes , B. J. , Bluestone , J. A. , Kruisbeek , A. , Maloy , W. L. , Coligan , J. E. and Schwartz , R. H.Differential expression of two distinct T‐cell receptors during thymocyte development . Nature 326 , 79 – 81 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 20. ) Thompson , S. D. , Manzo , A. R. , Pelkonen , J. , Larche , M. and Hurwitz , J. L.Developmental T‐cell receptor gene rearrangements: relatedness of the α/β and γ/δ T‐cell precursor . Eur. J. Immunol. 21 , 1939 – 1950 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 21. ) Iwasato , T. and Yamagishi , H.Novel excision products of T cell receptor gamma gene rearrangements and developmental stage specificity implied by the frequency of nucleotide insertions at signal joints . Eur. J. Immunol. 22 , 101 – 106 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 22. ) Muto , M. , Kubo , E. , Sado , T. , Shimizu , T. and Yamagishi , H.Characterization and clonality of prelymphoma cells of B10 mice treated with fractionated X‐irradiation (FX) . In “ Proceedings of International Conference on Radiation Effects and Protection ,” pp. 198 – 205 ( 1992. ). JAERI Press; , Tokyo . [Google Scholar]
- 23. ) Zakut‐Houri , R. , Givol , D. , Bienz , B. , Rogel , A. and Oren , M.Structure and expression of the genes encoding the murine p53 cellular tumor antigen . In “ CSH Conferences on Cell Proliferation and Cancer ,” Vol. 11 , pp. 393 – 401 ( 1984. ). Cold Spring Harbor Laboratory Press; , New York . [Google Scholar]
- 24. ) Sasaki , M.Current status of cytogenetic studies in animal tumors with special reference to nonrandom chromosome changes . Cancer Genet. Cytogenet. 5 , 153 – 172 ( 1982. ). [DOI] [PubMed] [Google Scholar]
- 25. ) Miller , D. A. and Miller , O. J.Chromosomes and cancer in the mouse: studies in tumor, established cell lines, and cell hybrids . Adv. Cancer Res. 39 , 153 – 182 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 26. ) McMorrow , L. E. , Newcomb , E. W. and Pellicer , A.Identification of a specific marker chromosome early in tumor development in γ‐irradiated C57BL/6J mice . Leukemia 2 , 115 – 119 ( 1988. ). [PubMed] [Google Scholar]
- 27. ) Chan , F. P. H. , Ball , J. K. and Sergovich , F. R.Trisomy #15 in murine thymomas induced by chemical carcinogens, X‐irradiation, and an endogenous murine leukemia virus . J. Natl. Cancer Inst. 62 , 605 – 610 ( 1975. ). [DOI] [PubMed] [Google Scholar]
- 28. ) Carbonell , F. , Eul , J. , Anselstetter , V. , Hameister , H. , Seidel , H. J. and Kreja , L.Trisomy 15 as a regular finding in chemically induced murine T‐cell leukemogenesis . Int. J. Cancer 39 , 534 – 537 ( 1987. ). [DOI] [PubMed] [Google Scholar]