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Carcinogenesis Advance Access published online on September 26, 2003
Carcinogenesis, doi:10.1093/carcin/bgg177
© 2003 by Oxford University Press
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© 2003 Oxford University Press

CARCINOGENESIS

The D5Mit7 locus on mouse chromosome 5 provides resistance to {gamma}-ray induced but not N-methyl-N-nitrosourea induced thymic lymphomas

Yasumitsu Kodama 1, Yoshihiro Yoshikai 2, Yasushi Tamura 2, Shigeharu Wakana 3, Ritsuo Takagi 4, Ohtsura Niwa 5, and Ryo Kominami 6*

1 Departments of Molecular Genetics and Oral Health Science, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachi 1-757, Niigata 951-8122, Japan
2 Department of Molecular Genetics, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachi 1-757, Niigata 951-8122, Japan
3 RIKEN Institute, Yokohama, Tozuka-Ku 244-0804, Japan
4 Department of Oral Health Science, 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
6 Department of Molecular Genetics, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachi 1-757, Niigata 951-8122; Center for Transdisciplinary Research, Niigata University, Asahimachi 1-757, Niigata 951-8122, Japan

* Corresponding author. E-mail: rykomina{at}med.niigata-u.ac.jp.

Received 3 July 2003 ; revised 27 August 2003 ; accepted 11 September 2003

Abstract

Susceptibility to {gamma}-ray induction of thymic lymphomas in mouse strains is controlled by low-penetrance genetic variant alleles. Our previous genome-wide scan of a mouse backcross between BALB/c and MSM strains suggested the existence of a BALB/c resistance locus near D5Mit5 on chromosome 5. To confirm this resistance, we produced congenic mice carrying a 28.4 cM region between D5Mit4 and D5Mit315 from the MSM parental strain on the BALB/c background. Lymphomas were induced in their progeny by {gamma}-ray irradiation or administration of N-methyl-N-nitrosourea (MNU), an alklating agent. The incidence of radiogenic lymphomas was 87.5% in mice of the M/M genotype at D5Mit7, significantly higher than the 46% incidence in mice of the C/M genotype, indicating highly significant linkage between the locus and the resistance (P=0.000054). In contrast, the frequencies of MNU induced thymic lymphomas were similar between the two genotypes (P=0.35 in {chi}2 test). These results confirm the presence of a resistance allele for {gamma}-ray induction of thymic lymphomas near the D5Mit7 locus and strongly suggest that this locus modifies carcinogenic risk from exposure to radiation but not to alkylating agents.

mouse thymic lymphomas, susceptibility/resistance, {gamma}-radiation, N-methyl-N-nitrosourea
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