Carcinogenesis Advance Access published online on January 30, 2004
Carcinogenesis, doi:10.1093/carcin/bgh094
© 2004 by Oxford University Press
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CARCINOGENESIS
1 Department of Molecular Genetics, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachi 1-757, Niigata 951-8122, Japan; Department of Regenerative and Transplant Medicine, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachi 1-757, Niigata 951-8122, Japan
* Corresponding author. E-mail: rykomina{at}med.niigata-u.ac.jp.
Received 5 November 2003
; revised 28 December 2003
; accepted 14 January 2004
Mouse thymic lymphomas induced by
mouse thymic lymphomas, Involvement of V(D)J recombinase in generation of intragenic deletions of Rit1/Bcl11b tumor suppressor gene in
-ray-induced thymic lymphomas and in normal thymus of the mouse
2 Department of Molecular Genetics, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachi 1-757, Niigata 951-8122, Japan
3 Department of Molecular Genetics, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachi 1-757, Niigata 951-8122, Japan; Center for transdisciplinary Research, Niigata University, Asahimachi 1-757, Niigata 951-8122, Japan
4 Department of Regenerative and Transplant Medicine, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachi 1-757, Niigata 951-8122, Japan
5 Radiation Biology Center, Kyoto University, Yoshida-Konoecho, Sakyou-Ku 606-8315, Kyoto, Japan
-irradiation exhibited homozygous deletions of the Rit1/Bcl11b tumor suppressor gene on chromosome 12 at high frequencies. Internal deletions of one allele were frequently accompanied by the loss of the other allele. In order to elucidate the mechanism of these internal deletions, the sites of breakage and rejoining were examined by PCR-mapping and sequencing. The 5' site of the deletions clustered within an approximately 5 kb region of intron 1 and the 3' site was confined to a site of intron 3. These sites contained P and/or N nucleotides and the cryptic sequences recognizable by the RAG1/2 recombinase in the vicinity. This suggests that the Rit1 intragenic deletions were generated by the endogenous illegitimate V(D)J recombinase activity and such aberrant recombination was also detected by nested PCR of DNA from the thymus of unirradiated mice but not of RAG2-deficient mice. Rough estimate indicated that there reside as many as 103 to 104 thymocytes having Rit1 deletions assuming the residence of 108 thymocytes in the thymus of unirradiated mice. Moreover, the recombination frequency was not affected by -irradiation. These results show no effect of radiation on Rit1 mutations and suggest an indirect mechanism for its role in lymphomagenesis.-radiation, N-methyl-N-nitrosourea, V(D)J recombinase, chromosomal deletion
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