Radiation-induced Cancer Cell Repopulation: A Possible Mechanism Implied by Experiments Using Transplantable Mouse-derived Sarcoma Cell Line

Cell Structure and Function

Rie Yamazaki³  Ken-ichiro Shibata⁴  Yusuke Miyai²  Hiroyuki Date³  Takeshi Nishioka³  Tsuguhide Takeshima¹  Masahiro Teduka⁵  Hiroki Shirato¹  Hisashi Haga²  Motoaki Yasuda⁴ 

[1] Department of Radiology, Hokkaido University Graduate School of Medicine;Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University;Department of Biomedical Sciences and Engineering, Faculty of Health Science, Hokkaido University;Department of Oral Pathological Sciences, Graduate School of Medicine, Hokkaido University;Resources and Energy Department, Hokkaido Industrial Research Institute

关键词: p16;    radiotherapy;    irradiation;    repopulation;    matrix metalloproteinase;   

DOI  :  10.1247/csf.10008

学科分类：分子生物学，细胞生物学和基因

来源: Japan Society for Cell Biology

【 摘 要 】

References(17)Cited-By(3)Purpose: 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. Materials and 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.

【 授权许可】

Unknown