| Co-Investigator(Kenkyū-buntansha) |
ONO Koji Research Reactor Institute, KYOTO UNIVERSITY, Professor, 原子炉実験所, 教授 (90122407)
HORI Hitoshi University of Tokushima, Department of Engineering, Professor, 工学部, 教授 (90119008)
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| Research Abstract |
Our method for detecting the quiescent (Q) cell response to γ-ray Irradiation using proliferating (P) cell labeling with BrdU and the MN frequency assay was also applicable to apoptosis detection assay. No radiosensitization effect upon combination treatment with paclitaxel (TXL) is induced in Q tumor cells. Consequently, the use of a bioreductive agent, tirapazamine (TPZ) as an additional agent is promising when solid tumors are treated with irradiation combined with TXL, due to its potent cytotoxicity to Q tumor cell fractions that are hard to radiosensitize by TXL. Combined treatments such as γ-ray irradiation or chemotherapy were combined or not, was useful for sensitizing tumor cells in vivo including Q cells even after an antianglogenic agent, TNP-470 treatment.
TPZ and cisplatin reduced the hypoxic fraction (HF) after treatment, especially In Q cells, and this tendency was particularly marked with TPZ. In contrast, bleomycin increased the HF after treatment. Both reoxygenation following γ-ray Irradiation or bleomycin treatment and a subsequent return to the pretreatment levels of HF following TPZ or cisplatin treatment (rehypoxfation) occurred more rapidly in total cells than in Q cells. Based on our previous report, we conclude that acute hypoxic cells play a major role in reoxygenation and rehypoxiation in SCC VII tumors. It was suggested that a newly developed ^<10>B containing a-amino alcohol of BPA, l-p-boronophenylalaninol-^<10>B (L-BPA-ol) has good potential as a ^<10>B-carrier in neutron capture therapy, especially when combined with both MTH and TPZ. Irrespective of p53 status of tumor cells, significant differences in radiosensitivity between total and Q tumor cells were consistently observed. From the viewpoint of tumor control as a whole including intratumor Q tumor cell control, a treatment modality for enhancing Q cell response has to be considered.
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