title: Persistent cell proliferation of terminal end buds precedes radiation-induced rat mammary carcinogenesis.
abstract: BACKGROUND
  The rat model of radiation-induced carcinogenesis is widely used to estimate breast cancer risk, but it is unknown whether mammary terminal end buds (TEBs), the hypothesized target of chemical carcinogens, are also targets of radiation-induced carcinogenesis.
  
  
  METHODS
  Female Sprague-Dawley rats were irradiated with X-rays (2 Gy). The morphology, bromodeoxyuridine (BrdU)-labelling index and pyknotic index of mammary ductal termini were investigated from 6 hours to 8 weeks post-irradiation.
  
  
  RESULTS
  The irradiated rats showed a significantly smaller decrease in TEB numbers than the controls 4-8 weeks after irradiation. The BrdU-labelling and pyknotic indices initially decreased and increased, respectively, recovered to control levels by 3 days post-irradiation, and remained significantly higher until 8 weeks and 4 weeks post-irradiation, respectively. One case of ductal hyperplasia was observed at 8 weeks.
  
  
  CONCLUSIONS
  Irradiation resulted in a persistent proliferation of TEBs, which may be associated with neoplastic transformation via a temporal differentiation arrest.
authors.affiliation: Low Dose Radiation Effects Research Project, Research Center for Radiation Safety, National Institute of Radiological Sciences, Chiba 263-8555, Japan. t_imaoka@nirs.go.jp
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Imaoka
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nishimura
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Shizuko
authors.initials: S
authors.lastname: Kakinuma
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Shimada
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D016923:Cell Death / Q000528:radiation effects; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D005260:Female; D007700:Kinetics; D008321:Mammary Glands, Animal / Q000503:physiopathology* / Q000528:radiation effects*; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014965:X-Rays / Q000009:adverse effects
chemical_list: D001973:Bromodeoxyuridine