Cytogenetic and cellular events during radiation-induced thymic lymphomagenesis in the p53 heterozygous (+/-) B10 mouse.
OBJECTIVE
Cellular and cytogenetic events in radiation-induced thymic lymphomagenesis were investigated in the p53 heterozygous (+/-) mouse following a single dose of whole-body irradiation.


METHODS
The loss of the wild-type p53 allele and microsatellite markers of chromosome 11 in thymic lymphomas that developed in the p53 heterozygous (+/-) mouse after irradiation, and the stage at which prelymphoma cells appeared were analysed.


RESULTS
The p53 heterozygous mouse developed thymic lymphomas in a dose-dependent manner. The loss of the wild-type p53 allele (loss of heterozygosity; LOH) occurred in almost all thymic lymphomas induced in the irradiated p53 heterozygous mouse. Cytogenetic analysis for the mechanism of LOH strongly suggested that the loss of the wild-type p53 gene in the lymphomas was caused by duplication of the disrupted allele through either homologous recombination or non-disjunctional chromosome duplication. The assay for prelymphoma cells suggested that a critical event in the development of prelymphoma cells occurred at least 3 weeks after irradiation.


CONCLUSIONS
The loss of the wild-type p53 gene in thymocytes of the p53 heterozygous mouse may precede the development of prelymphoma cells after irradiation and be a valuable marker of radiation-induced leukemogenesis.
Tanaka
K
K
Radiation Hazards Research Group, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage, Chiba 263-8555, Japan.
Watanabe
K
K
Mori
M
M
Kamisaku
H
H
Tsuji
H
H
Hirabayashi
Y
Y
Inoue
T
T
Yoshida
K
K
Aizawa
S
S
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D016026:Bone Marrow Transplantation; D003582:Cytogenetics; D016158:Genes, p53; D006579:Heterozygote; D019656:Loss of Heterozygosity; D016399:Lymphoma, T-Cell / Q000209:etiology* / Q000235:genetics* / Q000517:prevention & control; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018895:Microsatellite Repeats; D009381:Neoplasms, Radiation-Induced / Q000209:etiology* / Q000235:genetics* / Q000517:prevention & control; D011230:Precancerous Conditions / Q000209:etiology / Q000235:genetics / Q000517:prevention & control; D013601:T-Lymphocytes / Q000276:immunology; D013953:Thymus Neoplasms / Q000209:etiology* / Q000235:genetics* / Q000517:prevention & control
D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; C028388:thymus-leukemia antigens