Direct detection of p53 -/- thymocyte appearing at an early stage of radiation-induced thymic lymphomagenesis in p53 +/- heterozygous B10 mice.
OBJECTIVE
The appearance of tumor suppressor protein 53 (p53) -/- thymocytes at an early stage of radiation-induced lymphomagenesis was investigated in the p53 heterozygous (+/-) B10 mice following a single dose of irradiation, since most thymic lymphomas manifested the loss of the wild-type p53 allele and the loss of heterozygosity was thought to be an early event critical for radiation-induced thymic lymphomagenesis in p53 +/- mice.


METHODS
The mice were exposed to a single dose (6 Gy) of irradiation to induce thymic lymphomas and, at various times after irradiation, treated with an extremely high dose (30 Gy) of whole-body irradiation to enrich p53 -/- thymocytes and, 24 h later, the remaining thymocytes were assayed for cell surface markers and p53 genotype.


RESULTS
In a significant fraction of the p53 +/- mice 5 weeks after 6 Gy irradiation, there was a relative increase in the number of cluster of differentiation (CD) 4+CD8+ thymocyte subpopulation among thymocytes remaining after 30 Gy irradiation. The CD4+CD8+ double-positive (DP) thymocytes were shown to contain p53-/- cells, and the number of p53 -/- thymocytes was more than 10(5) in those individuals.


CONCLUSIONS
The results clearly indicated that an extremely high dose (30 Gy) of whole-body irradiation enabled us to directly detect p53 -/- thymocytes in an abundant p53 +/- thymocyte population and that proliferative p53 -/- thymocytes develop in a CD4+CD8+ DP thymocyte subpopulation within a few weeks after a single dose (6 Gy) of irradiation.
Aizawa
Shiro
S
Radiation Hazards Research Group, National Institute of Radiological Sciences, Inage, Chiba, Japan. aizawa@nirs.go.jp
Tanaka
Kaoru
K
Mori
Masahiko
M
Tsuji
Satsuki
S
Yoshida
Kazuko
K
D000818:Animals; D004307:Dose-Response Relationship, Radiation; D008214:Lymphocytes / Q000378:metabolism* / Q000528:radiation effects*; D008223:Lymphoma / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009381:Neoplasms, Radiation-Induced / Q000378:metabolism* / Q000473:pathology; D011829:Radiation Dosage; D013953:Thymus Neoplasms / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014916:Whole-Body Irradiation
D016159:Tumor Suppressor Protein p53