| Co-Investigator(Kenkyū-buntansha) |
FURUTA Masakazu Osaka Prefecture University, Research Institute for Advanced Science and Technology, 先端科学研究所, 講師 (40181458)
SUGIMOTO Kenji Osaka Prefecture University, Graduate School of Agriculture and Biological Sciences, 農学生命科学研究科, 教授 (40196746)
MORI Nobuko Osaka Prefecture University, Research Institute for Advanced Science and Technology, 先端科学研究所, 講師 (90100221)
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| Research Abstract |
To investigate effects of heterozygous deficient p53 (p53^<+/->) and/or Atm (Atm^<+/->) genes in mammaly tumorigenesis, we examined the tumor induction by X-inadiation and spontaneous development of the tumors in p53^<+/-> and/or Aim^<+/-> (BALB/cHeA x MSM/Ms) F_1 female mice. The p53^<+/-> efficiently developed mammaly carcinomas (MC) in both Atm^<+/+> and Atm^<+/-> mice. Histopathological features of the MC did not differ between Atm^<+/+> and Atm^<+/-> mice, and also between irradiated and non-irradiated groups. Atm-heterozygous deficiency enhanced development of MC in p53-heterozygous knockout mice. Both the ratio of MC-bearing mice and average MC number per mouse in p53^<+/+> Atm^<+/-> group were significantly larger than those in p53^<+/-> Atm^<+/+> mice. Almost all p53^<+/+> mice did not develop the MC in spite of Aim gene status. X-irradiation of 5 Gy at 5 weeks of age considerably shortened latent period of the MC development Irradiation also induced lymphomas efficiently regardless of genotypes of p53 and Atm, while some lymphomas were observed in non-iimdiated mice.
To examine possible contributions of individual tumor suppressor genes to radiation mammary carcinogenesis, we have investigated the loss of heterozygosity (LOH). Frequencies of LOH in MC were 30%, 52%, 20% 28%, 57% and 65% on chromosomes 5,8,9,10,11 and 12, respectively. We found frequent LOH in 2 regions on chromosome 12. One region is located near ceniromere. The frequency of LOH reached 60%. The other region includes D12Mit132(52cM), and frequency of LOH was about 56%. Frequent allele losses were also found in this region of lymphomas. Notable LOH was also observed at D9Mit20(60cM)(20%) and D10Mit7(43cM)(36%) in the MC. However, wild allele of Atm on chromosome 9 was retained.
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