Journal Article

The <i>D5Mit7</i> locus on mouse chromosome 5 provides resistance to γ-ray-induced but not <i>N</i>-methyl-<i>N</i>-nitrosourea-induced thymic lymphomas

Yasumitsu Kodama, Yoshihiro Yoshikai, Yasushi Tamura, Shigeharu Wakana, Ritsuo Takagi, Ohtsura Niwa and Ryo Kominami

in Carcinogenesis

Volume 25, issue 1, pages 143-148
Published in print January 2004 | ISSN: 0143-3334
Published online January 2004 | e-ISSN: 1460-2180 | DOI:
The D5Mit7 locus on mouse chromosome 5 provides resistance to γ-ray-induced but not N-methyl-N-nitrosourea-induced thymic lymphomas

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Susceptibility to γ-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 γ-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 χ2 test). These results confirm the presence of a resistance allele for γ-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.

Keywords: MNU, N-methyl-N-nitrosourea

Journal Article.  4568 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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