2003年5月
Effects of p53 Status and Wortmannin Treatment on Potentially Lethal Damage Repair, with Emphasis on the Response of Intratumor Quiescent Cells
Radiation Medicine - Medical Imaging and Radiation Oncology
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- 巻
- 21
- 号
- 3
- 開始ページ
- 120
- 終了ページ
- 127
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
Purpose: To examine the effects of p53 status and wortmannin treatment on potentially lethal damage repair, referring to the response of intratumor quiescent cells. Methods: Human head and neck squamous cell carcinoma cells transfected with mutant TP53 (SAS/mp53) or with neo vector as a control (SAS/neo) were injected subcutaneously into both hind legs of Balb/cA nude mice. Mice bearing the tumors received 5-bromo-2′-deoxyuridine (BrdU) continuously to label all proliferating (P) cells in the tumors. The mice then received γ-rays with or without subsequent wortmannin administration. Right after or 24 h after γ-ray irradiation alone or 24 h after wortmannin administration following irradiation, the tumors were excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with a cytokinesis blocker (cytochalasin-B), and the micronucleus (MN) frequency in cells without BrdU labeling [quiescent (Q) cells] was determined using immunofluorescence staining for BrdU. The MN frequency in total (P+Q) tumor cells was determined from the tumors that were not pretreated with BrdU. Results: On the whole, larger values of MN frequency and surviving fraction were observed in SAS/mp53 cells than in SAS/neo cells, and Q cells showed lower MN frequencies than total cells. Without wortmannin, SAS/neo tumor cells, especially Q cells within SAS/neo tumors, showed large potentially lethal damage repair (PLDR) capacities, compared with total or Q tumor cells within SAS/mp53 tumors that showed little PLDR capacity. Wortmannin treatment inhibited the PLDR in SAS/neo tumors very effectively, but showed no apparent effect on either total or Q tumor cells within SAS/mp53 tumors. Conclusion: PLDR in vivo was thought to be a p53-dependent event whether in total or Q tumor cell populations.
- リンク情報
- ID情報
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- ISSN : 0288-2043
- J-Global ID : 200902231491286079
- CiNii Articles ID : 10013917533
- PubMed ID : 12868860
- SCOPUS ID : 0344010495