The D5Mit7 locus on mouse chromosome 5 provides resistance to γ-ray-induced but not N-methyl-N-nitrosourea-induced thymic lymphomas
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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DOI：
10.1093/carcin/bgg177
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发表时间：
2004-01-01
期刊：
影响因子：
4.7
通讯作者：
Kominami，R
中科院分区：
文献类型：
--
作者：
Kodama，Y;Yoshikai，Y;Kominami，R
小鼠品系中胸腺淋巴瘤对γ射线诱导的易感性受低频率遗传变异等位基因控制。我们以前的全基因组扫描BALB/c和MSM品系之间的小鼠回交表明，存在一个BALB/c的耐药位点附近的D5 Mit 5的5号染色体上。为了证实这种抗性，我们在BALB/c背景下从MSM亲本品系产生了携带D5 Mit 4和D5 Mit 315之间28.4cM区域的同源小鼠。通过γ射线照射或给予烷化剂N-甲基-N-亚硝基脲（MNU）诱导其子代淋巴瘤。D5 Mit 7位点M/M基因型小鼠的放射性淋巴瘤发病率为87.5%，显著高于C/M基因型小鼠的46%，表明该位点与耐药性之间存在高度显著的连锁关系（P= 0.000054）。而MNU基因型与非MNU基因型胸腺淋巴瘤发生率无显著性差异（χ 2检验P= 0.35）。这些结果证实了在D5 Mit 7位点附近存在γ射线诱导胸腺淋巴瘤的抗性等位基因，并强烈表明该位点改变了辐射暴露的致癌风险，但不改变烷化剂的致癌风险。
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 nearD5Mit5on chromosome 5. To confirm this resistance, we produced congenic mice carrying a 28.4 cM region betweenD5Mit4andD5Mit315from the MSM parental strain on the BALB/c background. Lymphomas were induced in their progeny by γ-ray irradiation or administration ofN-methyl-N-nitrosourea (MNU), an alkylating agent. The incidence of radiogenic lymphomas was 87.5% in mice of the M/M genotype atD5Mit7, 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 χ2test). These results confirm the presence of a resistance allele for γ-ray induction of thymic lymphomas near theD5Mit7locus and strongly suggest that this locus modifies carcinogenic risk from exposure to radiation but not to alkylating agents.