部長室

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Updated 2016.09.20

変異遺伝部長 本間 正充(ほんま まさみつ) honma@nihs.go.jp

専門:細胞遺伝学、分子生物学、毒性学

現在の研究テーマ:
・構造活性相関による遺伝毒性の予測
・ほ乳類におけるDNA二本鎖切断修復機構
・遺伝毒性化学物質の発がんリスク評価

研究関連発表資料

  1. 2011年11月 日本環境変異原学会 シンポジウム
    「ICH S2の概要および遺伝毒性研究における発がん性の意味」
  2. 2012年11月 日本環境変異原学会 シンポジウム
    「遺伝毒性を如何に評価、解釈するのか?」
  3. 2013年2月 日化協 セミナー
    「変異原性QSAR」
  4. 2013年7月 衛研 シンポジウム
    「遺伝毒性の予測とリスク評価」
  5. 2013年11月 国際環境変異原学会(ブラジル)
    「Risk Assessment and Management of Genotoxic Impurities in Pharmaceuticals」
  6. 2014年9月ISPE-ADI設定セミナー(東京)
    「ICH-M7; 医薬品中に含まれる遺伝毒性(変異原性)不純物の安全性評価とTTCの考え方」
  7. 2014年12月アジア環境変異原学会(インド・コルカタ)
    「Tracing the Fate of Site-Specifically Introduced DNA Damage in the Human Genome」
  8. 2015年5月インド環境変異原学会(インド・インパール)
    「Trend and Progress of OECD Genotoxicity Testing Guidelines」
  9. 2015年11月 環境変異原学会(福岡)
    「①学会賞講演 部位特異的損傷をゲノム中に導入したヒト細胞における突然変異誘発機構の研究」
  10. 「②シンポジウム 遺伝毒性ガイドライン」
  11. 2016年4月 第13回医薬品評価フォーラム(東京)
    「ICH-M7ガイドラインの概要と今後の取り組み」
  12. QSAR2016(米国・フロリダ)
    「Ames/QSAR International Collaborative Study」
  13. AMES/QSAR page

略歴

学歴:
1983年 千葉大学薬学部薬学科卒業
1989年 東京大学大学院医学研究科博士課程修了
医学博士

職歴:
1989年 がん研究振興財団リサーチレジデント
1991年 国立医薬品食品衛生研究所・変異遺伝部 研究員
1993年 ハーバード大学・衛生学部 客員研究員(1年)
1999年 国立医薬品食品衛生研究所・変異遺伝部第一室 室長
2012年 国立医薬品食品衛生研究所・変異遺伝部 部長

審議会等(主なもの)

独立行政法人医薬品医療機器総合機構専門委員

独立行政法人医薬品医療機器GLP評価委員

医薬食品局安衛法変異原性試験結果検討委員

医薬食品局化審法GLP評価委員

食品安全委員会新開発食品等専門調査会専門委員

食品安全委員会農薬専門調査会専門委員

学術研究活動

アジア環境変異原学会(AAEMS) 理事

米国環境変異ゲノム学会(EMGS)理事

米国環境変異ゲノム学会(EMGS)学会誌(Environ. Mol. Mutagen)編集委員

英国環境変異原学会(UKEMS)学会誌(Mutagenesis) 編集委員

中国食品医薬品検定研究院(中国・北京) 客員教授

中国科学院上海薬物研究所(中国・上海) 客員教授

四川大学華西衛生学院(中国・成都) 客員教授

宇宙航空研究開発機構(JAXA)宇宙科学研究所 客員教授

大阪大学大学院薬学研究科 招へい教授

国際活動

ICH-M7(遺伝毒性不純物)日本規制側トピックリーダー

OECD遺伝毒性試験ガイドライン策定 専門委員

国際環境保健研究所(HESI)・遺伝毒性技術委員会 運営委員

国際遺伝毒性試験ワークショップ 運営委員

研究業績(2012-)

  1. Suzuki T, Yasui M, Honma M. Mutator phenotype and DNA double-strand break repair in BLM helicase-deficient human cells. Mol Cell Biol. [Epub ahead of print] (2016)
  2. Suzuki T, Grúz P, Honma M, Adachi N, Nohmi T. The role of DNA polymerase ζ in translesion synthesis across bulky DNA adducts and cross-links in human cells. Mutat Res. [Epub ahead of print] (2016)
  3. Sassa A, Kanemaru Y, Kamoshita N, Honma M, Yasui M. Mutagenic consequences of cytosine alterations site-specifically embedded in the human genome. Genes Environ. 38,17 (2016)
  4. Cao Y, Yang L, Feng N, Shi O, Xi J, You X, Yin C, Yang H, Horibata K, Honma M, Qian B, Weng W, Luan Y. A population study using the human erythrocyte PIG-A assay. Environ Mol Mutagen. [Epub ahead of print](2016)
  5. Sugiyama KI, Furusawa H, Shimizu M, Grúz P, Honma M. Epigenetic mutagen as histone modulator can be detected by yeast flocculation. Mutagenesis. [Epub ahead of print] (2016)
  6. Manganelli S, Benfenati E, Manganaro A, Kulkarni S, Barton-Maclaren TS, Honma M. New quantitative structure-activity relationship models improve predictability of Ames mutagenicity for aromatic azo compounds. Toxicol Sci. [Epub ahead of print] (2016)
  7. 本間正充 ゲノム上に起きたDNA損傷の運命をターゲットミュータジェネシスにより追跡する.日本がん疫学・分子疫学研究会 News Letter 114, 11-12 (2016)
  8. 本間正充 食品添加物等の遺伝毒性リスク評価法.食品衛生学雑誌 57(1)J12-J15 (2016)
  9. Suzuki T, Grúz P, Honma M, Adachi N, Nohmi T. Sensitivity of human cells expressing low-fidelity or weak-catalytic-activity variants of DNA polymerase ζ to genotoxic stresses. DNA Repair (Amst) 45. 34-43 (2016)
  10. Petko I. Petkov, Terry W. Schultz, E. Maria Donner, Masamitsu Honma, Takeshi Morita, Shuichi Hamada, Akihiro Wakata, Masayuki Mishima, Jiro Maniwa, Milen Todorov, Elena Kaloyanova, Stefan Kotov, Ovanes G. Mekenyan, Integrated Approach to Testing and Assessment for Predicting Rodent Genotoxic Carcinogenesity, Journal of Applied Toxicology [Epub ahead of print] (2016)
  11. E. Benfenati, M. Belli, T. Borges, E. Casimiro, J. Cester, A. Fernandez, G. Gini, M. Honma, M. Kinzl, R. Knauf, A. Manganaro, E. Mombelli, M. I. Petoumenou, M. Paparella, P. Paris & G. Raitano, Results of a round-robin exercise on read-across. SAR and QSAR in Environmental Research 27, 371-384 (2016)
  12. Horibata K, Ukai A, Honma M., Evaluation of mutagenicity of acrylamide using RBC Pig-a and PIGRET assays by single peroral dose in rats. Mutat Res. in press (2016)
  13. Masumura K, Toyoda-Hokaiwado N, Ukai A, Gondo Y, Honma M, Nohmi T. Estimation of the frequency of inherited germline mutations by whole exome sequencing in ethyl nitrosourea-treated and untreated gpt delta mice. Gene & Environ. 38, 10 (2016)
  14. Morita T, Hamada S, Masumura K, Wakata A, Maniwa J, Takasawa H, Yasunaga K, Hashizume T, Honma M. Evaluation of the sensitivity and specificity of in vivo erythrocytemicronucleus and transgenic rodent gene mutation tests to detect rodent carcinogens. Mutat. Res. 802, 1-29 (2016)
  15. Ahlberg E, Amberg A, Beilke LD, Bower D, Cross KP, Custer L, Ford KA, Van Gompel J, Harvey J, Honma M, Jolly R, Joossens E, Kemper RA, Kenyon M, Kruhlak N, Kuhnke L, Leavitt P, Naven R, Neilan C, Quigley DP, Shuey D, Spirkl HP, Stavitskaya L, Teasdale A, White A, Wichard J, Zwickl C, Myatt GJ. Extending (Q)SARs to incorporate proprietary knowledge for regulatory purposes: A case study using aromatic amine mutagenicity. Regul Toxicol Pharmacol. 13, 1-12 (2016)
  16. Amberg A, Beilke L, Bercu J, Bower D, Brigo A, Cross KP, Custer L, Dobo K, Dowdy E, Ford KA, Glowienke S, Van Gompel J, Harvey J, Hasselgren C, Honma M, Jolly R, Kemper R, Kenyon M, Kruhlak N, Leavitt P, Miller S, Muster W, Nicolette J, Plaper A, Powley M, Quigley DP, Reddy MV, Spirkl HP, Stavitskaya L, Teasdale A, Weiner S, Welch DS, White A, Wichard J, Myatt GJ. Principles and procedures for implementation of ICH M7 recommended (Q)SAR analyses. Regul Toxicol Pharmacol. 77, 13-24 (2016)
  17. Honma, M., Evaluation of the in vivo genotoxicity of Allura Red AC (Food Red No. 40). Food and Chemical Toxicology. 84, 270-275 (2015)
  18. Masumura K, Sakamoto Y, Kumita W, Honma M, Nishikawa A, Nohmi T: Genomic integration of lambda EG10 transgene in gpt delta transgenic rodents. Genes and Environment. 37, 24 (2015)
  19. Sassa, A., Kamoshita, N., Kanemaru, Y., Honma, M., and Yasui, M., Xeroderma Pigmentosum Group A Suppresses Mutagenesis Caused by Clustered Oxidative DNA Adducts in the Human Genome. PLoS ONE. 10(11) (2015)
  20. 本間正充:第1章 ICH M7の適用範囲と既存ガイドラインとの関連性 「ICH M7 変異原性不純物の開発段階からの評価・管理と申請/CTD記載法」サイエンステクノロジー (2015)
  21. 本間正充:1.3遺伝毒性試験法「衛生試験法・注解」金原出版格式会社(日本薬学会編)(2015)
  22. Barber C, Amberg A, Custer L, Dobo KL, Glowienke S, Van Gompel J, Gutsell S, Harvey J, Honma M, Kenyon MO, Kruhlak N, Muster W, Stavitskaya L, Teasdale A, Vessey J, Wichard J., Establishing best practise in the application of expert review of mutagenicity under ICH M7. Regul Toxicol Pharmacol. 73, 367-377 (2015)
  23. Canipa S, Cayley A, Drewe WC, Williams RV, Hamada S, Hirose A, Honma M, Morita T. Using in vitro structural alerts for chromosome damage to predict in vivo activity and direct future testing. Mutagenesis. (2015)
  24. Kanemaru Y, Suzuki T, Niimi N, Grúz P, Matsumoto K, Adachi N, Honma M, Nohmi T. Catalytic and non-catalytic roles of DNA polymerase κ in the protection of human cells against genotoxic stresses. Environ Mol Mutagen. (2015)
  25. Keka IS, Mohiuddin, Maede Y, Rahman MM, Sakuma T, Honma M, Yamamoto T, Takeda S, Sasanuma H. Smarcal1 promotes double-strand-break repair by nonhomologous end-joining. Nucleic Acids Res. 43, 6359-72 (2015)
  26. Uno Y, Kojima H, Omori T, Corvi R, Honma M, Schechtman LM, Tice RR, Beevers C, Boeck MD, Burlinson B, Hobbs CA, Kitamoto S, Kraynak AR, McNamee J, Nakagawa Y, Pant K, Plappert-Helbig U, Priestley C, Takasawa H, Wada K, Wirnitzer U, Asano N, Escobar PA, Lovell D, Morita T, Nakajima M, Ohno Y, Hayashi M. JaCVAM-organized international validation study of the in vivo rodent alkaline comet assay for detection of genotoxic carcinogens: II. Summary of definitive validation study results. Mutat Res Genet Toxicol Environ Mutagen. 786-788:45-76 (2015)
  27. Morita T, Uno Y, Honma M, Kojima H, Hayashi M, Tice RR, Corvi R, Schechtman L. The JaCVAM international validation study on the in vivo comet assay: Selection of test chemicals. Mutat Res Genet Toxicol Environ Mutagen. 786-788, 14-44 (2015)
  28. Uno Y, Kojima H, Omori T, Corvi R, Honma M, Schechtman LM, Tice RR, Burlinson B, Escobar PA, Kraynak AR, Nakagawa Y, Nakajima M, Pant K, Asano N, Lovell D, Morita T, Ohno Y, Hayashi M. JaCVAM-organized international validation study of the in vivo rodent alkaline comet assay for the detection of genotoxic carcinogens: I. Summary of pre-validation study results. Mutat Res Genet Toxicol Environ Mutagen. 786-788:3-13 (2015)
  29. Hamada S, Ohyama W, Takashima R, Shimada K, Matsumoto K, Kawakami S, Uno F, Sui H, Shimada Y, Imamura T, Matsumura S, Sanada H, Inoue K, Muto S, Ogawa I, Hayashi A, Takayanagi T, Ogiwara Y, Maeda A, Okada E, Terashima Y, Takasawa H, Narumi K, Wako Y, Kawasako K, Sano M, Ohashi N, Morita T, Kojima H, Honma M, Hayashi M. Evaluation of the repeated-dose liver and gastrointestinal tract micronucleus assays with 22 chemicals using young adult rats: summary of the collaborative study by the Collaborative Study Group for the Micronucleus Test (CSGMT)/The Japanese Environmental Mutagen Society (JEMS) – Mammalian Mutagenicity Study Group (MMS). Mutat Res Genet Toxicol Environ Mutagen. 780-781:2-17 (2015)
  30. Yasui M, Kamoshita N, Nishimura T, Honma M; Mechanism of induction of binucleated cells by multiwalled carbon nanotubes as revealed by live-cell imaging analysis. Genes and Environment 37, 6 (2015)
  31. Martusa HJ, Hayashi M, Honma M, Kasper P, Gollapudi B, Mueller L, Schoeny R, Uno Y, Kirkland DJ, Summary of major conclusions from the 6th International Workshop on Genotoxicity Testing (IWGT), Foz do Iguacu, Brazil, Mutat. Res., 783, 1-5 (2015)
  32. Yauk CL, Aardema MJ, Benthem VJ, Bishop JB, Dearfield KL, DeMarini DM, Dubrova YE, Honma M, Lupski JR, Marchetti F, Meistrich ML, Pacchierotti F, Stewart J, Waters MD, Douglas GR. Approaches for Identifying Germ Cell Mutagens: Report of the 2013 IWGT Workshop on Germ Cell Assays. Mutat. Res., 783, 36-54 (2015)
  33. Petko I. Petkov, Grace Patlewicz, Terry W. Schultz, Masamitsu Honma, Milen Todorov, Stefan Kotov, Sabcho D. Dimitrov, Maria Donner, Ovanes G. Mekenyan, A feasibility study: Can information collected to classify for mutagenicity be informative in predicting carcinogenicity? Regul. Tox. Pharm., 72, 17-25 (2015)
  34. Zeiger E, Gollapudi B, Aardema MJ, Auerbach S, Boverhof D, Custer L, Dedon P, Honma M, Ishida S, Kasinski AL, Kim JH, Manjanatha MG, Marlowe J, Pfuhler S, Pogribny I, Slikker W, Stankowski LF Jr, Tanir JY, Tice R, van Benthem J, White P, Witt KL, Thybaud V. Opportunities to integrate new approaches in genetic toxicology: an ILSI-HESI workshop report. Environ Mol Mutagen. 56, 277-85 (2015)
  35. Sugiyama, K., Takamune, M., Furusawa, H., and Honma, M., Human DNA methyltransferase gene-transformed yeasts display an inducible flocculation inhibited by 5-aza-20-deoxycytidine. Biochemical and Biophysical Research Communications 456, 689–694 (2015)
  36. Onami S, Cho Y, Toyoda T, Horibata K, Ishii Y, Umemura T, Honma M, Nohmi T, Nishikawa A, and Ogawa K. Absence of in vivo genotoxicity of 3-monochloropropane-1,2-diol and associated fatty acid esters in a 4-week comprehensive toxicity study using F344 gpt delta rats. Mutagenesis, 29, 295-302 (2014)
  37. Horibata K, Ukai A, Honma M., Evaluation of rats' in vivo genotoxicity induced by N-ethyl-N-nitrosourea in the RBC Pig-a, PIGRET, and gpt assays. Genes and Enviromment, 36,199-202 (2014)
  38. Matsumoto, M., Masumori, S., Hirata-Koizumi, M., Ono, A., Honma, M., Yokoyama, K. and Hirose, A., Evaluation of in vivo mutagenicity of hydroquinone in Muta™ mice. Mutat Res Genet Toxicol Environ Mutagen., 775-776, 94-98 (2014)
  39. Morita, T., Miyajima, A., Hatano, A., Honma, M.: Effects of the proposed top concentration limit on an in vitro chromosomal aberration test to assay sensitivity or to reduce the number of false positives, Mutation Research, 769, 34–49 (2014)
  40. Yasui M, Kanemaru Y, Kamoshita N, Suzuki T, Arakawa T, Honma M. Tracing the fates of site-specifically introduced DNA adducts in the human genome. DNA Repair 15, 11-20 (2014)
  41. Sassa A, Suzuki T, Kanemaru Y, Niimi N, Fujimoto H, Katafuchi A, Grúz P, Yasui M, Gupta RC, Johnson F, Ohta T, Honma M, Adachi N, Nohmi T. In vivo evidence that phenylalanine 171 acts as a molecular brake for translesion DNA synthesis across benzo[a]pyrene DNA adducts by human DNA polymerase κ. DNA Repair 15, 21-28 (2014)
  42. 本間正充 安全性に関するトピックの動向 M7:潜在的発がんリスクを低減するための医薬品中DNA反応性(変異原性)不純物の評価及び管理 医薬品医療機器レギュラトリーサイエンス44,1010-1015(2013)
  43. Hayashi M, Honma M, Takahashi M, Horibe A, Tanaka J, Tsuchiya M, Morita T, Identification and Evaluation of Potentially Genotoxic Agricultural and Food-related Chemicals. Food Safety 1, 32-42 (2013)
  44. Horibata K, Ukai A, Kimoto T, Suzuki T, Kamoshita N, Masumura K, Nohmi T, Honma M. Evaluation of in vivo genotoxicity induced by N-ethyl-N-nitrosourea,benzo[a]pyrene, and 4-nitroquinoline-1-oxide in the Pig-a and gpt assays. Environ Mol Mutagen. 54, 747-754 (2013)
  45. Kimura A, Miyata A, Honma M. A combination of in vitro comet assay and micronucleus test using human lymphoblastoid TK6 cells. Mutagenesis. 28, 583-90 (2013)
  46. Stefan Pfuhler, Rosalie Elespuru, Marilyn Aardema, Shareen H. Doak, E. Maria Donner, Masamitsu Honma, Micheline Kirsch-Volders, Robert Landsiedel, Mugimane Manjanatha, Tim Singer, James H. Kim, Genotoxicity of Nanomaterials: Refining Strategies and Tests for Hazard Identification. Environ Mol. Mutagen. 54, 229-239 (2013)
  47. Sassa A, Kamoshita N, Matsuda T, Ishii Y, Kuraoka I, Nohmi T, Ohta T, Honma M, Yasui M, Miscoding properties of 8-chloro-2'-deoxyguanosine, a hypochlorous acid-induced DNA adduct, catalysed by human DNA polymerases, Mutagenesis 28, 81-88 (2013)
  48. Kimoto T, Horibata K, Chikura S, Hashimoto K, Itoh S, Sanada H, Muto S, Uno Y, Yamada M, Honma M. Interlaboratory trial of the rat Pig-a mutation assay using an erythroid marker HIS49 antibody. Mutation Research, 755, 126-34 (2013)
  49. 本間正充:第II編 薬物評価におけるin silico手法の活用、第4章 変異原性の予測―医薬品中に存在する不純物の評価― 「In vitro毒性・動態評価の最前線」シーエムシー出版(小島肇夫監修)2013年
  50. 本間正充:第14章 ほ乳類細胞を用いたin vitro小核試験 「動物実験代替安全性試験プロトコル集」シーエムシー出版(小島肇夫監修)2012年
  51. Honma M, Takahashi T, Asada S, Nakagawa Y, Ikeda A, Yamakage K. In vitro clastogenicity and phototoxicity of fullerene (C(60)) nanomaterials in mammalian cells. Mutat Res. 749, 97-100 (2012)
  52. Nohmi T, Honma M, Yamada M, Masumura K, Yasui M, Horibata K, Fukushima S. 2nd International Symposium on Genotoxic and Carcinogenic Thresholds. Gene and Environment 34, 141-143 (2012)
  53. Zhang X, Horibata K, Saijo M, Ishigami C, Ukai A, Kanno S, Tahara H, Neilan EG, Honma M, Nohmi T, Yasui A, Tanaka K. Mutations in UVSSA cause UV-sensitive syndrome and destabilize ERCC6 in transcription-coupled DNA repair. Nat Genet. 44, 593-597 (2012)
  54. Ono A, Takahashi M, Hirose A, Kamata E, Kawamura T, Yamazaki T, Sato K, Yamada M, Fukumoto T, Okamura H, Mirokuji Y, Honma M. Validation of the (Q)SAR combination approach for mutagenicity prediction of flavor chemicals. Food Chem Toxicol. 50, 1536-1546 (2012)
  55. Yatagai F, Honma M., Ukai A, Omori K, Suzuki H, Shimazu T, Takahashi A, Ohnishi T, Dohmae , and Ishioka N. Preliminary results of space experient: Implication for the effects of space radiation and microgravity on survival and mutation induction in human cells. Ad. In Space Res. 49, 479-486 (2012)
  56. Morita T, Honma M, Morikawa K. Effect of reducing the top concentration used in the in vitro chromosomal aberration test in CHL cells on the evaluation of industrial chemical genotoxicity. Mutat. Res. 741, 32-56 (2012)
  57. Mekenyan OG, Petkov P, Kotov S, Stoeva S, Kamenska VB, Dimitrov S, Honma M, Hayashi M, Benigni R, Donner M, Patlewicz GY. Investigating the relationship between in vitro - in vivo genotoxicity: Derivation of mechanistic QSAR models for in vivo liver genotoxicity and in vivo bone marrow micronucleus formation which encompass metabolism. Chem Res Toxicol. 25, 277-296 (2012)

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