Genetic loci controlling susceptibility to γ-ray-induced thymic lymphoma

Abstract

is a susceptible strain for the development of gray induced mouse thymic lymphoma whereas MSM shows resistance. Association analysis of 220 backcross mice between the two strains using 67 markers was carried out to identify loci involved in the control of susceptibility. The genotype of mice with lymphoma showed excess heterozygosity relative to MSM homozygosity at D2Mit15 and D4Mit12 and was skewed toward MSM-derived alleles at D5Mit5. The P values in Mantel-Cox test were 0.0048 (D2Mit15), 0.0034 (D4Mit12) and 0.0048 (D5Mit5), suggesting association at the three loci in the susceptibility. Cooperative e ect on lymphomagenesis was also observed among the three loci. To obtain independent evidence for linkage at D4Mit12, we made partially congenic mice in which a D4Mit12 region in BALB/c was replaced by MSMderived homolog. Examination for the lymphoma susceptibility in 78 progeny of the congenic mice con®rmed the e ect of the locus near D4Mit12 (P=0.0037). The result, together with the linkage analysis, shows that the locus near D4Mit12 is regarded as a con®rmed linkage but the other two loci as marginally suggestive. Oncogene (2001) 20, 5243 ± 5247.

Genomic instability in radiation-induced mouse lymphoma from p53 heterozygous mice

“…Genetic background is known to affect the latency of radiation-induced mouse lymphomas (Saito et al, 2001) and an effect of genetic background has also been demonstrated on susceptibility to the heritable effects of radiation exposure (Watson et al, 1997). We therefore investigated an additional set of about 40 tumors from p53 þ /À (129/Sv  C57BL/6) F1 hybrids that show, on average, a longer latency than those from pure 129/Sv animals.…”

Nested Case-control Study of Occupational Radiation Exposure and Breast and Esophagus Cancer Risk among Medical Diagnostic X Ray Workers in Jiangsu of China

“…Although the radiation does not play so prominent role as chemical carcinogen in all human cancer causes, due to the application of nuclear technology in human production and life, especially in medical diagnosis and treatment field occupies a more and more special position, the potential hazards of radiation on humans are increasing. Therefore, research on the relationship between radiation and cancer has been the oncology, radiation biology, radiation protection and epidemiological research focus (Thompson et al, 1994;Sun et al, 1996;Yu et al, 2001;Wang et al, 2002 (Hattori et al, 1988;Yoshida et al, 1997;Nishimura et al, 1999;Saito et al, 2001). However, due to the presence of species, individual and organization-specific genetic differences, it is not yet established in vitro study using the theoretical model to evaluate its relationship with human tumors.…”

Predisposition to mouse thymic lymphomas in response to ionizing radiation depends on variant alleles encoding metal-responsive transcription factor-1 (Mtf-1)

“…Our previous association study of g-ray-induced thymic lymphomas in backcross mice between BALB/c and MSM and in congenic mice demonstrated the presence of the susceptibility locus near D4Mit12; the BALB/c allele exhibited a dominance or codominance over the MSM allele (Saito et al, 2001). This BALB/c allele also provided susceptibility to MNU-induced thymic lymphomas (Sato et al, 2003).…”

“…A congenic mouse line for D4Mit12 on chromosome 4 was obtained previously (Saito et al, 2001), which carried an MSM-derived chromosomal region spanning D4Mit9 and D4Mit203 (40 Mb). The original congenic mice were crossed with BALB/c mice and four subcongenic lines were obtained after genotyping with 15 microsatellite markers within this region.…”

“…We previously carried out a genome-wide scan of susceptibility to thymic lymphomas that induced by g-irradiation in backcross and congenic mice between a susceptible BALB/c strain and a resistant MSM strain (Saito et al, 2001). Results indicated the existence of a major BALB/ c susceptibility allele near D4Mit12 on chromosome 4.…”