The bystander effect observed in boron neutron capture therapy

• Project/Area Number: 17591266
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Radiation science
• Research Institution: Kyoto University
• Principal Investigator: KINASHI Yuko Kyoto University, Research Reactor Institute, Assistant Professor (80252534)
• Project Period (FY): 2005 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥3,730,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
• Keywords: micronucleus / lymphocyte / boron neutron capture therapy / acute radiation effect / α粒子 / 突然変異 / ホウ素化合物

Research Abstract

Evaluation of micronucleus induction in lymphocytes of patients following Boron-Neutron-Capture-Therapy
(1) A comparison with thyroid cancer patients treated with radioiodine
This study evaluated micronuclei induction in peripheral T-lymphocytes after BNCT (boron neutron capture therapy) irradiation of brain tumor and head-and-neck cancer patients. In all of these patients, the micronucleus frequency increased after BNCT; the number of micronuclei per 1000 binucleated T-lymphocytes after BNCT increased by 33.0±12.2 for brain tumor patients and 22.8±10.3 for head-and-neck cancer patients. In comparison to 14 thyroid cancer patients administered radioiodine (3.3-5.6 GBq) treatment, the frequency of micronuclei after internal radioiodine therapy increased to 105.0±30.5 per 1000 binucleated T-lymphocytes for thyroid cancer patients; thereafter, the increased micronucleus frequency of BNCT patients was less than one-third that seen for thyroid cancer patients after radioiodine treatment
(2) A comparison with X-ray radiotherapy
The evidence of acute radiation effect was studied based on a questionnaire answered by the chief physician. In an in-vitro neutron radiation study, we observed standard dose-response model induction and calculated the maximal biological dose estimation as 0.24 Gy-eq for head and neck tumor patients and 0.20 Gy-eq for brain tumor patients. The total body radiation dose obtained by biological estimation using the micronucleus assay correlated with the total effective dose of BNCT obtained by thermal neutron fluence and TLD estimation. The increased micronucleus frequency in BNCT patients was less than one-third of that in malignant tumor patients after X-ray radiotherapy.
These findings (1 and 2) demonstrate the usefulness of BNCT for selective high-LET radiotherapy, in association with a low irradiation effect of cytological radiation damage after BNCT, which provides a high tumor target dose for each cancer patient.

Research Products

• [Journal Article] ホウ素中性子捕捉療法後の末梢血リンパ球におけるマイクロヌクレウスの出現頻度の評価 (2008)
  • Author(s): 木梨友子、櫻井良憲、増永慎一郎、鈴木実、永田憲司、小野公二
  • Journal Title: 日本放射線腫瘍学会誌 20 Pages: 23-28
  • NAID: 10027060919
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] The bystandar effect observed in boron neutron capture therapy: a study of the induction of mutations in the HPRT locus (2008)
  • Author(s): Y. Kinashi, S. Masunaga, M. Suzuki, K. Nagata, S. Takahashi, K. Ono
  • Journal Title: International Journal of Radiation Oncology, Biology, Physics 68 Pages: 508-514
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Radiobiologic significance of response of intratumor quiescent cells to accelated carbon ion beams compared with gamma-rays and reactor neutron beams (2008)
  • Author(s): S. Masunaga, K Ando, A Uzawa, R Hirayama, Y Furusawa, S Koike, Y Sakurai, K. Nagata, M. Suzuki, G. Kashino, Y. Kinashi, H Tanaka, A Maruhashi and K. Ono
  • Journal Title: International Journal of Radiation Oncology, Biology, Physics 70 Pages: 221-228
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Biological dosimetry using micronucleus assay of lymphocytes for BNCT patients (2008)
  • Author(s): Y., Kinashi, Y., Sakurai, S., Masunaga, M., Suzuki, K., Nagata, K., Ono
  • Journal Title: J.Jpn.Soc.Ther.Radiol.Oncol 20 Pages: 23-28
  • NAID: 10027060919
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Radiobiologic significance of response of intratumor quiescent cells to accelated carbon ion beams compared with gamma-rays and reactor neutron beams (2008)
  • Author(s): S., Masunaga, K., Ando, A., Uzawa, R., Hirayama, Y., Furusawa, S., Koike, Y., Sakurai, K., Nagata, M., Suzuki, G., Kashino, Y., Kinashi, H., Tanaka, A., Maruhashi, K.,Ono
  • Journal Title: International Journal of Radiation Oncology, Biology, Physics 70 Pages: 221-228
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] ホウ素中性子捕捉療法後の末梢血リンパ球におけるマイクロヌクレウスの出現頻度の評価 (2008)
  • Author(s): 木梨友子、櫻井良憲、増永慎一郎、鈴木実、永田憲司、小野公二
  • Journal Title: 日本放射線腫瘍学会誌 20(1)(印刷中)
  • NAID: 10027060919
  • Peer Reviewed
• [Journal Article] Evaluation of micronucleus induction in lymphocytes of patients following Boron-Neutron-Capture-Therapy: A comparison with thyroid cancer patients treated with radioiodine (2007)
  • Author(s): Y. Kinashi, S. Masunaga, Y. Sakurai, M. Suzuki, K. Nagata and K. Ono
  • Journal Title: Journal of Radiation Research 48 Pages: 197-204
  • NAID: 110006278194
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Inhibition of repair if radiation-induced damage by mild temperature hyperthermia, reffering to the effect on quiescent cell popurations (2007)
  • Author(s): S. Masunaga, K. Nagata, M. Suzuki, G. Kashino, Y. Kinashi, H Tanaka, A Maruhashi and K. Ono
  • Journal Title: Radiation Medicine 25 Pages: 417-425
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Effective suppression of bystander effects by DMSO treatment of irradiated CHO cells. (2007)
  • Author(s): Kashino G, Prise KM, Suzuki K, Matsuda N, Kodama S, Suzuki M, Nagata K, Kinashi Y, Masunaga S, Ono K, Watanabe M.
  • Journal Title: Journal of Radiation Research 48 Pages: 327-333
  • NAID: 110006343945
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] First attempt of boron neutron capture therapy(BNCT)for hepatocellular carcinoma. (2007)
  • Author(s): M. Suzuki, Y. Sakurai, S. Hagiwara, S. Masunaga, Y. Kinashi, K. Nagata, A. Maruhashi, M. Kudo, K. Ono
  • Journal Title: Japanese Journal of Clinical Oncology 37 Pages: 376-381
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] A preliminary experimental study of boron neutron capture therapy for malignant tumors sreading in thoracic cavity (2007)
  • Author(s): M. Suzuki, Y. Sakurai, S. Masunaga, Y. Kinashi, K. Nagata, A. Maruhashi K. Ono
  • Journal Title: Japanese Journal of Clinical Oncology 37 Pages: 245-259
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] The bystandar effect observed in boron neutron capture therapy : a study of the induction of mutations in the HPRT locus (2007)
  • Author(s): Y., Kinashi, S., Masunaga, M., Suzuki, K., Nagata, S., Takahashi, K., Ono
  • Journal Title: International Journal of Radiation Oncology, Biology, Physics 68 Pages: 508-514
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Evaluation of micronucleus induction in lymphocytes of patients following Boron-Neutron-Capture-Therapy : A comparison with thyroid cancer patients treated with radioiodine (2007)
  • Author(s): Y., Kinashi, S., Masunaga, Y., Sakurai, M., Suzuki, K., Nagata, K., Ono
  • Journal Title: Journal of Radiation Research 48 Pages: 197-204
  • NAID: 110006278194
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Dependency of rapair of radiation-induced damage on p53 status and efficient inhibition of the repair with wortmannin treated in vivo, with reference to the effect on intratumor quescent cell popuration (2007)
  • Author(s): S., Masunaga, A., Takahashi, K., Ohnishi, K., Nagata, M., Suzuki, G., Kashino, Y., Kinashi, T., Ohnishi, K., Ono
  • Journal Title: Oncology Reports 18 Pages: 1589-1596
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inhibition of repair if radiation-induced damage by mild temperature hyperthermia, reffering to the effect on quiescent cell popurations (2007)
  • Author(s): S., Masunaga, K., Nagata, M., Suzuki, G., Kashino, Y., Kinashi, H., Tanaka, A., Maruhashi, K., Ono
  • Journal Title: Radiation Medicine 25 Pages: 417-425
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Effective suppression of bystander effects by DMSO treatment of irradiated CHO cells (2007)
  • Author(s): Kashino, G., Prise KM., Suzuki, K., Matsuda, N., Kodama, S., Suzuki, M., Nagata, K., Kinashi, Y., Masunaga, S., Ono, K., Watanabe, M
  • Journal Title: Journal of Radiation Research 48 Pages: 327-333
  • NAID: 110006343945
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] First attempt of boron neutron capture therapy (BNCT) for hepatocellular carcinoma A preliminary experimental study of boron neutron capture therapy for malignant tumors sreading in thoracic cavity (2007)
  • Author(s): M., Suzuki, Y., Sakurai, S., Hagiwara, S., Masunaga, Y., Kinashi, K., Nagata, A., Maruhashi, M., Kudo, K., Ono
  • Journal Title: Japanese Journal of Clinical Oncology 37 Pages: 376-381
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Evaluation of micronucleus induction in lymphocytes of patients following Boron-Neutron-Capture-Therapy: A comparison with thyroid cancer patients treated with radioiodine (2007)
  • Author(s): Yuko Kinashi, Shinichiro Masunaga, Yoshinori Sakurai, Minoru Suzuki, Kenji Nagata and Koji Ono
  • Journal Title: Journal of Radiation Research 48(3) Pages: 197-204
  • NAID: 110006278194
  • Peer Reviewed
• [Journal Article] The bystandar effect observed in boron neutron capture therapy: a study of the induction of mutations in the HPRT locus (2007)
  • Author(s): Yuko Kinashi, Shinichiro Masunaga, Minoru Suzuki, Kenji Nagata and Koji Ono
  • Journal Title: International Journal of Radiation Oncology, Biology, Physoics 68(2) Pages: 508-514
  • Peer Reviewed
• [Journal Article] Evaluation of micronucleus induction in lymphocytes of patients following Boron-Neutron-Capture-Therapy : A comparison with thyroid cancer patients treated with radioiodine (2007)
  • Author(s): Yuko Kinashi, Shinichiro Masunaga, Yoshinori Sakurai, Minoru Suzuki, Kenji Nagata, Koji Ono
  • Journal Title: Journal of Radiation Research (in press)(未定)
  • NAID: 110006278194
• [Journal Article] The bystandar effect observed in boron neutron capture therapy : a study of the induction of mutations in the HPRT locus (2007)
  • Author(s): Yuko Kinashi, Shinichiro Masunaga, Minoru Suzuki, Kenji Nagata, Koji Ono
  • Journal Title: International Journal of Radiation Oncology, Biology, Physics (in press)(未定)
• [Journal Article] The usefulness of a continuous administration of tirepazamine combined with reduced dose-rate irradiation using gamma-rays or reactor thermal neutrons (2006)
  • Author(s): S.Masunaga, Y.Sakurai, K.Nagata, M.Suzuki, A.Maryhashi, Y.Kinashi, H.Nagasawa, Y.Uto, H.Hori, K.Ono
  • Journal Title: British Journal of Radiology 79・948 Pages: 991-998
• [Journal Article] The potential of transferrin-pendant-type polyethyleneglycol liposomes encapsulation decahydrodecaborate-B-10 (GB-10)as B-10-carriers for boron neutron capture therapy (2006)
  • Author(s): SI.Masunaga, S.Kataoka, M.Maruyama, D.Nigg, Y.Sakurai, K.Nagata, M.Suzuki, Y.Kinashi, A.Maryhashi, K.Ono
  • Journal Title: International Journal of Radiation Oncology, Biology, Physics 66・5 Pages: 1515-1522
• [Journal Article] Impact of intra-arterial administration of boron ompounds on dose-volume histgrams in boron neutron capture therapy for recurrent head-and-neck tumors (2006)
  • Author(s): M.Suzuki, Y.Sakurai, K.Nagata, Y.Kinashi, S.Masunaga, K.Ono, A.Maruhashi, I.Kato, N.Fuwa, J.Hiratsuka, Y.Imahori
  • Journal Title: International Journal of Radiation Oncology, Biology, Physics 66・5 Pages: 1523-1527
• [Journal Article] Feastibility of boron neutron capture therpy (BNCT) for malignant pleural mesotherioma from a viewpoint of dose distribution analysis (2006)
  • Author(s): M.Suzuki, Y.Sakurai, S.Masunaga, Y.Kinashi, K.Nagata, A.Maruhashi, K.Ono
  • Journal Title: International Journal of Radiation Oncology, Biology, Physics 66・5 Pages: 1584-1589
• [Journal Article] Evaluation of hipoxia-specific cytotoxic bioreductive agent-sodium bicaptate-10B conjugates as 10B-carriers in boron neutron capture therapy (2006)
  • Author(s): Shin-ichiro Masunaga, Hideko Nagasawa, Yoshinori Sakurai, Yoshihiro Uto, Hitoshi Hori, Kenji Nagata, Minoru Suzuki, Akira Maruhashi, Yuko Kinashi, Koji Ono
  • Journal Title: Radiation Medicine 24・2 Pages: 98-107
• [Journal Article] Evaluation of hipoxic cell radio-sensitizers in terms of radio-sensitizers and repair-inhibiting potential. Dependency on p53 status of tumor cells and the effects on intratumor quiescent cells (2006)
  • Author(s): Shin-ichiro Masunaga, Yoshihiro Uto, Hideko Nagasawa, Hitoshi Hori, Kenji Nagata, Minoru Suzuki, Yuko Kinashi, Koji Ono
  • Journal Title: Anticancer Research 26・2A Pages: 1261-1270
• [Journal Article] The usefulness of mild temperature hyperthermia combined with a newly developed hypoxia-oriented 10B conjugate compound, TX-2100, for boron neutron capture therapy
  • Author(s): Shin-ichiro Masunaga, Hideko Nagasawa, Yoshinori Sakurai, Yoshihiro Uto, Hitoshi Hori, Kenji Nagata, Minoru Suzuki, Akira Maruhashi, Yuko Kinashi, Koji Ono
  • Journal Title: International Journal of Hyperthermia (in press)(未定)
• [Presentation] ビタミンC配糖体負荷によるマウス脾細胞における放射線照射後のアポトーシス抑制効果と抗酸化酵素活性の変化 (2007)
  • Author(s): 木梨友子、増永慎一郎、鈴木実、菓子野元郎、小野公二
  • Organizer: 日本放射線影響学会第50回大会
  • Place of Presentation: 千葉幕張メッセ
  • Year and Date: 2007-11-14
• [Presentation] BNCTのための基礎研究と臨床応用 (2007)
  • Author(s): 木梨友子
  • Organizer: (独)放射線医学総合研究所 第2回粒子線生命科学研究会シンポジウム
  • Place of Presentation: 千葉
  • Year and Date: 2007-11-13
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Basic and clinical research for Boron-Neutron-Capture-Therapy (2007)
  • Author(s): Yuko, Kinashi
  • Organizer: The 2th Symposium of the assosiation for ion-beam life science in National Institute of Radiological Sciences
  • Place of Presentation: Chiba
  • Year and Date: 2007-11-13
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 中性子捕捉療法におけるバイスタンダー効果により誘発された突然変異に対する防護剤の効果 (2007)
  • Author(s): 木梨友子、増永慎一郎、鈴木実、菓子野元郎、小野公二
  • Organizer: 第4回日本中性子捕捉療法学会学術大会
  • Place of Presentation: 大阪
  • Year and Date: 2007-08-26
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] The effect of radioprotectants observed in mutagenesis induced the bystander effect following BNCT (2007)
  • Author(s): Yuko, Kinashi, Shinnichiro, Masunaga, Minoru, Suzuki, Genro, Kashino, Koji, Ono
  • Organizer: The 4th congress of Japan Boron-Neutron-Capture-Therapy Society
  • Place of Presentation: Osaka
  • Year and Date: 2007-08-26
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] ビタミンC配糖体による放射線照射後の抗酸化酵素の変化 横浜 (2007)
  • Author(s): 木梨友子、鈴木実、永田憲司、増永慎一郎、小野公二
  • Organizer: 第65回日本医学放射線学会学術集会
  • Place of Presentation: 横浜
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] ビタミンC配糖体負荷によるマウス脾細胞における放射線照射後のアポトーシス抑制効果と抗酸化酵素活性の変化 (2007)
  • Author(s): 木梨友子、鈴木実、菓子野元郎、増永慎一郎、小野公二
  • Organizer: 日本放射線影響学会第50回大会
  • Place of Presentation: 千葉
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Evaluation of anti-oxidative enzymes following irradiation with ascorbic acid glycoside treatment (2007)
  • Author(s): Yuko, Kinashi, Minoru, Suzuki, Kennji, Nagata, Shinnichiro, Masunaga, Koji, Ono
  • Organizer: The 65th congress of Japan Radiological Society
  • Place of Presentation: Yokohama
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] L-ascorbic acid 2-glicoside protected apoptosis induction of mouse splenocytes following total body irradiation (2007)
  • Author(s): Yuko, Kinashi, Shinichiro, Masunaga, Minoru, Suzuki, Genro, Kashino, Koji, Ono
  • Organizer: The 50th annual meeting of the Japan Radiation Research Society
  • Place of Presentation: Chiba
  • Description: 「研究成果報告書概要(欧文)」より