Abstract
To investigate effects of heterozygous deficient p53 (p53+/-) and/or Atm (Atm+/-) genes in radiation-induced mammary tumorigenesis, we examined the tumor induction by X-irradiation in p53+/- and/or Atm+/-- (BALB/cHeA x MSM/Ms) F1 female mice. Both p53+/-Atm+/- and p53+/-Atm+/+ mice efficiently developed mammary adenocarcinomas (MC) by X-irradiation of 5 Gy at 5 weeks of age and the incidences of the MC were 58% and 24%, respectively. Average number of MC per mouse in p53+/-Atm+/- group was significantly larger than that in p53+/-Atm+/+ mice. X-irradiation considerably shortened latent period of the MC development. These MC were observed early in irradiated group (during 25 to 43 weeks of age) compared with non-irradiated group (during 45 to 60 weeks of age). However, almost all irradiated p53+/+ mice did not develop the MC in spite of Atm gene status. To analyze putative tumor suppressor genes in mammary carcinogenesis, we examined loss of heterozygosity (LOH) in the MC. Frequent LOH was observed on chromosomes 5, 8, 10, 11 and 12. Precise allelotype analyses on chromosomes 8, 10 and 12 have been performed. Examination of RNA expression of some candidate genes are in progress.
