title: Cytogenetic analysis of radiation-induced leukemia in Trp53-deficient C3H/He mice.
abstract: C3H/He mice develop acute myeloid leukemia (AML) after whole-body irradiation, but the strain becomes highly susceptible to stem cell leukemia (SCL) when a null mutation is introduced into the Trp53 gene. To examine the etiology of SCL and the influence of chromosomal instability on leukemogenesis, 12 SCLs and two AMLs arising from Trp53-deficient C3H/He mice were investigated cytogenetically. Each SCL demonstrated cell-to-cell variation in the number and structural integrity of their chromosomes, indicating chromosomal instability. Typical deletion of chromosome 2 was observed in the two AML cases, while most SCL cells did not display this aberration. Deletions and rearrangements of chromosome 11 were noticeable in SCLs from Trp53 heterozygotes but not in AMLs. Analysis of loss of heterozygosity revealed that aberrations involving chromosome 11 in SCLs resulted in loss of the wild-type Trp53 allele. These results suggest that loss of Trp53 function triggers the tumorigenic process leading toward SCL through the induction of chromosomal instability, and that SCL and AML are distinct varieties of leukemia.
authors.affiliation: Oita University of Nursing and Health Sciences, 2944-9 Megusuno, Notsuharu, Oita-gun, Oita 870-1201, Japan. ban@oita-nhs.ac.jp
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Ban
authors.forename: Kazuko
authors.initials: K
authors.lastname: Yoshida
authors.forename: Shiro
authors.initials: S
authors.lastname: Aizawa
authors.forename: Sachiko
authors.initials: S
authors.lastname: Wada
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kai
mesh_terms: D000208:Acute Disease; D000483:Alleles; D000818:Animals; D002875:Chromosomes / Q000528:radiation effects; D005260:Female; D017404:In Situ Hybridization, Fluorescence; D007951:Leukemia, Myeloid / Q000235:genetics; D007953:Leukemia, Radiation-Induced / Q000473:pathology*; D019656:Loss of Heterozygosity / Q000528:radiation effects; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014916:Whole-Body Irradiation
chemical_list: D016159:Tumor Suppressor Protein p53