title: Radiation-induced cancer cell repopulation: a possible mechanism implied by experiments using transplantable mouse-derived sarcoma cell line.
abstract: OBJECTIVE
  Treatment with any cytotoxic agent can trigger surviving cells in a tumor to divide faster than before. This phenomenon is widely recognized as "repopulation". To better clarify the mechanism, gene expression profiling and pathological experiments were performed.
  
  
  METHODS
  A mouse fibrosarcoma cell line, QRsP, was used. Cells were irradiated with 10 Gy. Colony assay and cloning were performed. Six clones were established. cDNA analysis was performed on the clone that showed the largest number of colonies on the 2nd 10 Gy irradiation. Mouse transplantation experiment was then carried out.
  
  
  RESULTS
  cDNA analysis showed that cyclin-dependent kinase inhibitors, p16 and p57 were down-regulated; 14.8- and 12.0-fold, respectively for the tolerant clone. Matrix metalloproteinase 3 and 13 were up-regulated; 22.5- and 25.8-fold, respectively. Transplantation ratio was 100% (5/5) for the tolerant clone whereas it was 40% (2/5) for the parent. Under light microscope, the mean mitotic cell number was 4.0+/-3.9 for the parent, and 12.8+/-3.4 for the tolerant clone (p<0.01, Student's t-test).
  
  
  CONCLUSIONS
  This study implies that repopulation is not a temporary reaction to irradiation. It is caused probably by "clonal" gene-expression changes, though it remains unknown whether the changes are attributable to tolerant cell selection or to gene mutation/modification.
authors.affiliation: Department of Biomedical Sciences and Engineering, Faculty of Health Science, Hokkaido University, N12-W5, Sapporo 060-0812, Japan. trout@hs.hokudai.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishioka
authors.forename: Motoaki
authors.initials: M
authors.lastname: Yasuda
authors.forename: Tsuguhide
authors.initials: T
authors.lastname: Takeshima
authors.forename: Hisashi
authors.initials: H
authors.lastname: Haga
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Miyai
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Shibata
authors.forename: Rie
authors.initials: R
authors.lastname: Yamazaki
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shirato
authors.forename: Masahiro
authors.initials: M
authors.lastname: Teduka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Date
mesh_terms: D000818:Animals; D002452:Cell Count; D002455:Cell Division / Q000528:radiation effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D005260:Female; D051379:Mice; D009368:Neoplasm Transplantation; D012509:Sarcoma / Q000473:pathology*