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Carcinogenesis Advance Access originally published online on September 26, 2003
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Carcinogenesis, Vol. 25, No. 1, 143-148, January 2004

CARCINOGENESIS

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

Yasumitsu Kodama1,2, Yoshihiro Yoshikai1, Yasushi Tamura1, Shigeharu Wakana4, Ritsuo Takagi2, Ohtsura Niwa5 and Ryo Kominami1,3,6

1 Department of Molecular Genetics and 2 Department of Oral Health Science, Graduate School of Medical and Dental Sciences and 3 Center for Transdisciplinary Research, Niigata University, Asahimachi 1-757, Niigata 951-8122, 4 RIKEN Institute, Yokohama, Tozuka-Ku 244-0804 and 5 Radiation Biology center, Kyoto University, Yoshida-Konoecho, Sakyou-Ku 606-8315, Kyoto, Japan

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 alkylating 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.


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