Risk assesment of chemical leukoderma

• Project/Area Number: 16K10152
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Institute for Developmental Research Aichi Developmental Disability Center (2017-2019); Nagoya University (2016)
• Principal Investigator: Iida Machiko 愛知県医療療育総合センター発達障害研究所, 障害モデル研究部, 研究員 (60465515)
• Co-Investigator(Kenkyū-buntansha): 加藤 昌志 名古屋大学, 医学系研究科, 教授 (10281073)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 白斑 / 毒性評価 / 皮膚疾患 / モデルマウス / 皮膚 / 毒性 / 色素細胞学

Outline of Final Research Achievements

Leukoderma is a skin disorder in which patchy hypopigmentation develops. Recently, more than 16,000 people in Asian countries developed chemical leukoderma due to the use of whitening agents containing 2% (w/w) rhododenol. Previous studies showed that 30% rhododenol caused leukoderma in animal experiments. However, the development of leukoderma caused by lower concentrations of chemicals such as 2% rhododenol, has not been reported. We demonstrated that external treatment with 2% rhododenol and 2% raspberry ketone caused the development of leukoderma in the tail skin of hairless mice with loss of epidermal melanocytes and melanin in the lesions. Thus, we developed a novel evaluation system that enables sensitive assessment of the risks of chemical leukoderma.

Academic Significance and Societal Importance of the Research Achievements

化学物質による白斑被害を未然に防ぐには、白斑毒性を高感度に検知できるシステムが求められる。本研究ではヒト類似皮膚をもつモデルマウスにこれまでの報告にはない低濃度（２％ロドデノール, ２％ラズベリーケトン）の化学物質を外用し白斑毒性が再現されるかを検討した。その結果、過去の皮膚毒性試験ではほとんど着目されることのなかった尾部皮膚において例外なく白斑を誘発することに成功した。モデルマウスの尾の皮膚を用いた本試験法は、化学物質による白斑毒性を高感度に検知できる新たな毒性評価法として有用である可能性がある。

Research Products

• [Journal Article] Peptides containing the MXXCW motif inhibit oncogenic RET kinase activity with a novel mechanism of action. (2020)
  • Author(s): Takeda K, Kawamoto Y, Nagasaki Y, Okuno Y, Goto Y, Iida M1, Yajima I, Ohgami N, Kato M.
  • Journal Title: Peptides containing the MXXCW motif inhibit oncogenic RET kinase activity with a novel mechanism of action. Volume: 10 Pages: 336-349
  • Peer Reviewed / Open Access
• [Journal Article] A unique system that can sensitively assess the risk of chemical leukoderma by using murine tail skin (2019)
  • Author(s): Iida Machiko、Tazaki Akira、Deng Yuqi、Chen Wei、Yajima Ichiro、Kondo-Ida Lisa、Hashimoto Kazunori、Ohgami Nobutaka、Kato Masashi
  • Journal Title: Chemosphere Volume: 235 Pages: 713-718
  • DOI: 10.1016/j.chemosphere.2019.06.185
  • NAID: 120006777551
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Inhibition of mast cell degranulation by melanin. (2019)
  • Author(s): Kawamoto Y, Kondo H, Hasegawa M, Kurimoto C, Ishii Y, Kato C, Botei T, Shinya M, Murate T, Ueno Y, Kawabe M, Goto Y, Yamamoto R, Iida M, Yajima I, Ohgami N, Kato M, Takeda K.
  • Journal Title: Biochem Pharmacol. Volume: 163 Pages: 178-193
  • DOI: 10.1016/j.bcp.2019.02.015
  • Peer Reviewed
• [Journal Article] Histological analysis of the skin of Abca1-deleted mice: A potential model for dry skin (2019)
  • Author(s): Deng Yuqi、Ohgami Nobutaka、Iida Machiko、Tazaki Akira、Intoh Atsushi、Kondo-Ida Lisa、Lu Rui、Tsuzuki Toyonori、Yokoyama Shinji、Kato Masashi
  • Journal Title: Eur J Dermatol Volume: 29 Issue: 5 Pages: 549-551
  • DOI: 10.1684/ejd.2019.3621
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Arsenic level in toenails is associated with hearing loss in humans. (2018)
  • Author(s): Li X, Ohgami N, Yajima I, Xu H, Iiida M, Ohino R, Ninomiya H, Shen D, Ahsan N, Akhand AA, Kato M
  • Journal Title: PLoS ONE Volume: 13 Issue: 7 Pages: e0198743-e0198743
  • DOI: 10.1371/journal.pone.0198743
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A comprehensive study including monitoring, assessment of health effects and development of a remediation method for chromium pollution (2018)
  • Author(s): Yoshinaga M, Ninomiya H, Al Hossain MMA, Sudo M, Akhand AA, Ahsan N, Alim MA, Khalequzzaman M, Iida M, Yajima I, Ohgami N, Kato M.
  • Journal Title: Chemosphere Volume: 201 Pages: 667-75
  • DOI: 10.1016/j.chemosphere.2018.03.026
  • NAID: 120006496424
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Increased expression level of Hsp70 in the inner ears of mice by exposure to low frequency noise. (2018)
  • Author(s): Ninomiya H, Ohgami N, Oshino R, Kato M, Ohgami K, Li X, Shen D, Iida M, Yajima I, Angelidis CE, Adachi H, Katsuno M, Sobue G, Kato M.
  • Journal Title: Hear Res Volume: - Pages: 49-54
  • DOI: 10.1016/j.heares.2018.02.006
  • NAID: 120006517664
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Loss of Stemness, EMT, and Supernumerary Tooth Formation in Cebpb-/-Runx2+/- Murine Incisors. (2018)
  • Author(s): Saito K, Takahashi K, Huang B, Asahara M, Kiso H, Togo Y, Tsukamoto H, Mishima S, Nagata M, Iida M, Tokita Y, Asai M, Shimizu A, Komori T, Harada H, MacDougall M, Sugai M, Bessho K.
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 5169-5169
  • DOI: 10.1038/s41598-018-23515-y
  • NAID: 120006545187
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Use of Anti-phospho-girdin Antibodies to Visualize Intestinal Tuft Cells in Free-Floating Mouse Jejunum Cryosections. (2018)
  • Author(s): Mizutani Y, Kuga D, Iida M, Ushida K, Takagi T, Tokita Y, Takahashi M, Asai M.
  • Journal Title: Journal of visualized experiments: JoVE Volume: 21 Issue: 133 Pages: 133-133
  • DOI: 10.3791/57475
  • Peer Reviewed / Open Access
• [Journal Article] Oral exposure to arsenic causes hearing loss in young people aged 12-29 years and in young mice. (2017)
  • Author(s): Li X, Ohgami N, Omata Y, Yajima I, Iida M, Oshino R, Ohnuma S, Ahsan N, Akhand AA, Kato M.
  • Journal Title: Sci Rep Volume: 7 Issue: 1 Pages: 6844-6844
  • DOI: 10.1038/s41598-017-06096-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Manganese-mediated decrease in levels of c-RET and tyrosine hydroxylase expression in vitro. (2017)
  • Author(s): Kumasaka MY, Yajima I, Ohgami N, Ninomiya H, Iida M, Li X, Oshino R, Tanihata H, Yoshinaga M, Kato M.
  • Journal Title: Neurotox Res Volume: 32 Issue: 4 Pages: 661-70
  • DOI: 10.1007/s12640-017-9783-0
  • NAID: 120006367974
  • Peer Reviewed
• [Journal Article] Arsenic-mediated hyperpigmented skin via NF-kappa B/Endothelin1 signaling in an originally developed hairless mouse model. (2017)
  • Author(s): Yajima I, Kumasaka MY, Iida M, Osino R, Tanihata H, Al Hossain A MM, Ohgami N, Kato M.
  • Journal Title: Arch Toxicol Volume: 91 Issue: 11 Pages: 3507-16
  • DOI: 10.1007/s00204-017-1975-0
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Arsenic levels in cutaneous appendicular organs are correlated with digitally evaluated hyperpigmented skin of the forehead but not the sole in Bangladesh residents. (2017)
  • Author(s): Yajima I, Ahsan N, Akhand AA, Al Hossain MA, Yoshinaga M, Ohgami N, Iida M, Oshino R, Naito M, Wakai K, Kato M.
  • Journal Title: Journal of Exposure Science & Environmental Epidemiology Volume: 28 Issue: 1 Pages: 64-68
  • DOI: 10.1038/jes.2016.70
  • NAID: 120006473550
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Noninvasive, label-free, three-dimensional imaging of melanoma with confocal photothermal microscopy: Differentiate malignant melanoma from benign tumor tissue. (2016)
  • Author(s): He J, Wang N, Tsurui H, Kato M, Iida M, Kobayashi T
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 30209-30209
  • DOI: 10.1038/srep30209
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] APPLICATION OF NON-THERMAL ATMOSPHERIC PRESSURE PLASMA IRRADIATION TO SPONTANEOUSLY DEVELOPED MELANOMA IN MICE (2017)
  • Author(s): Machiko Iida, Yasuhiro Omata, Takehito Kajiwara, Ichiro Yajima, Masaru Hori, Masashi Kato
  • Organizer: International Conference on Plasma Medical Science Innovation (ICPMSI) 2017
  • Place of Presentation: Nagoya University（愛知県名古屋市）
  • Year and Date: 2017-02-27
  • Int'l Joint Research / Invited
• [Presentation] メラノーマ自然発症モデルマウスにおける非熱プラズマの発癌予防効果 (2016)
  • Author(s): 飯田真智子、小又尉広、矢嶋伊知朗、加藤祐貴、長谷川まり、中野千尋、鄒存超、李香、大神信孝、加藤昌志
  • Organizer: 第86回日本衛生学会学術総会
  • Place of Presentation: 旭川市民文化会館（北海道旭川市）
  • Year and Date: 2016-05-11
• [Presentation] 動物モデルを用いた紫外線による健康リスクの多角的評価 (2016)
  • Author(s): 李香、鄒存超、矢嶋伊知朗、大神信孝、加藤昌志
  • Organizer: 第86回日本衛生学会学術総会
  • Place of Presentation: 旭川市民文化会館（北海道旭川市）
  • Year and Date: 2016-05-11
• [Remarks] 愛知県医療療育総合センター 発達障害研究所
  • URL: https://www.pref.aichi.jp/addc/eachfacility/hattatsu/department/index5.html
• [Remarks] 名古屋大学大学院医学系研究科 環境労働衛生学ホームページ
  • URL: https://www.med.nagoya-u.ac.jp/hygiene/
• [Remarks] 名古屋大学大学院医学系研究科環境労働衛生学 ホームページ
  • URL: https://www.med.nagoya-u.ac.jp/hygiene/
• [Patent(Industrial Property Rights)] 白斑毒性及び黒皮症毒性の試験方法 (2016)
  • Inventor(s): 加藤昌志、飯田真智子
  • Industrial Property Rights Holder: 国立大学法人名古屋大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-104698
  • Filing Date: 2016-05-25