A molecular epidemiological study to explore arsenic relation carcinogenesis and malignant progression in an arsenic endemic rural region in Shanxi province of China

2012 Fiscal Year Final Research Report

• Project/Area Number: 22406006
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 海外学術
• Research Field: Human pathology
• Research Institution: Suzuka University of Medical Science
• Principal Investigator: MA Ning 鈴鹿医療科学大学, 保健衛生学部, 教授 (30263015)
• Co-Investigator(Kenkyū-buntansha): KAWANISHI Shosuke 鈴鹿医療科学大学, 薬学部, 教授 (10025637) ; INOUE Sumiko 鈴鹿医療科学大学, 薬学部, 准教授 (20378657) ; OHNISHI Shiho 鈴鹿医療科学大学, 薬学部, 助手 (80511914) ; MURATA Mariko 三重大学, 医学研究科, 教授 (10171141)
• Project Period (FY): 2010 – 2012
• Keywords: ヒ素 / 発がん / 臨床疫学 / がん幹細胞 / ニトロ化ストレス / HaCaT 細胞 / バイ オマーカー / リスク評価

Research Abstract

We demonstrated that 8-OHdG was generated in polymorphonuclear leukocytes (PMN). The 8-OHdG in PMN was observed in all investigated populations, while it was frequently found along with the elevated amounts of cell debris in individuals with skin lesion including hypopigmentation and keratosis in arsenic exposed participants of Shanxi province, China. After the human skin cell line (HaCaT) was exposed to an environmentally relevant level of arsenic 0.05 ppm for about 4 months, we determined the8-nitroguanine and cancer stem cell marker CD44v6 in the acquired cancer phenotype. Treated cells with arsenic became apparently tumorigenic, that pathological studies of xenograft tumor in nude mice showed highly undifferentiated tumors.

Research Products

• [Journal Article] Oxidative DNA damage of peripheral blood polymorphonuclear leukocytes, selectively induced by chronic arsenic exposure, is associated with extent of arsenic-related skin lesions. (2013)
  • Author(s): Pei Q, Ma N, Zhang J, Xu W, Li Y, Ma Z, Li Y, Tian F, Zhang W, Mu J, Li Y, Wang D, Liu H, Yang M, Ma C, Yun F.
  • Journal Title: Toxicol Appl Pharmacol. Volume: 266(1) Pages: 143-149
  • DOI: DOI:10.1016/j.taap.2012.10.031.
  • Peer Reviewed
• [Journal Article] CD44v6 expression in human skin keratinocytes as a possible mechanism for carcinogenesis associated with chronicarsenic exposure. (2013)
  • Author(s): Huang S, Guo S, Guo F, Yang Q, Xiao X, Murata M, Ohnishi S, Kawanishi S, Ma N
  • Journal Title: European Journal of Histochemistry. Volume: 57(1) Pages: e1
  • DOI: DOI:10.4081/ejh.2013.e1
  • Peer Reviewed
• [Journal Article] Maternal high-fat diets cause insulin resistance through inflammatory changes in fetal adipose tissue. (2013)
  • Author(s): Murabayashi N, Sugiyama T, Zhang L, Kamimoto Y, Umekawa T, Ma N, Sagawa N.
  • Journal Title: Eur J Obstet Gynecol Reprod Biol. Volume: (13)00089-4 Pages: S0301-2115
  • DOI: DOI:10.1016/j.ejogrb
  • Peer Reviewed
• [Journal Article] Protection by taurine against iNOS-dependent DNA damage in heavily exercised skeletal muscle by inhibition of the NF-kappaB signaling pathway. (2013)
  • Author(s): Sugiura H, Shinya S, Okita S, Kato T, Naka T, Kawanishi S, Ohnishi S, Oshida Y, Ma N
  • Journal Title: Advances in Experiemtntal Medicine and Biology. Volume: 775 Pages: 237-246
  • DOI: DOI:10.1007/978-1-4614-6130-2_20
  • Peer Reviewed
• [Journal Article] Role of nitrative and oxidative DNA damage in inflammation-related carcinogenesis (2012)
  • Author(s): Murata M, Thanan R, Ma N, Kawanishi S
  • Journal Title: Journal of Biomedicine and Biotechnology Volume: 2012 Pages: 623019
  • DOI: DOI:10.1155/2012/623019
  • Peer Reviewed
• [Journal Article] Promoter hypermethylation of Ras-related GTPase gene RRAD inactivates a tumor suppressor function in nasopharyngeal carcinoma (2012)
  • Author(s): Mo Y, Midorikawa K, Zhang Z, Zhou X, Ma N, Huang G, Hiraku Y, Oikawa S, Murata M
  • Journal Title: Cancer Letter Volume: 323(2) Pages: 147-54
  • DOI: DOI:10.1016/j. canlet.2012.03.042
  • Peer Reviewed
• [Journal Article] Nitrative DNA damage induced by multi-walled carbon nanotube via endocytosis in human lung epithelial cells (2012)
  • Author(s): Guo F, Ma N, Horibe Y, Kawanishi S, Murata M, Hiraku Y
  • Journal Title: Toxicol Appl. Pharmacol Volume: 260(2) Pages: 183-192
  • DOI: DOI:10.1016/j. taap.2012.02.010.
  • Peer Reviewed
• [Journal Article] Inflammation-induced protein carbonylation contributes to poor prognosis for cholangiocarcinoma. (2012)
  • Author(s): Thanan R, Oikawa S, Yongvanit P, Hiraku Y, Ma N, Pinlaor S, Pairojkul C,Wongkham C, Sripa B, Khuntikeo N, Kawanishi S, Murata M.
  • Journal Title: Free Radic Biol Med. Volume: 52(8) Pages: 1465-1472
  • DOI: DOI:10.1016/j.freeradbiomed.2012.01.01
  • Peer Reviewed
• [Journal Article] Nuclear localization of COX-2 in relation to the expression of stemness markers in urinary bladder cancer. (2012)
  • Author(s): Thanan R, Murata M, Ma N, Hammam O, Wishahi M, El Leithy T, Hiraku Y, Oikawa S, Kawanishi S.
  • Journal Title: Mediators Inflamm. Volume: 165879
  • DOI: DOI:10.1155/2012/165879.
  • Peer Reviewed
• [Journal Article] Proton pump inhibitors suppress iNOS-dependent DNA damage in Barrett's esophagus by increasing Mn-SOD expression. (2012)
  • Author(s): Thanan R, Ma N, Iijima K, Abe Y, Koike T, Shimosegawa T, Pinlaor S, Hiraku Y, OikawaS, Murata M, Kawanishi S.
  • Journal Title: Biochem Biophys Res Commun. Volume: 421(2) Pages: 280-285
  • DOI: doi:10.1016/j.bbrc.2012.03.152
  • Peer Reviewed
• [Journal Article] Arsenic-induced inhibition of hippocampal neurogenesis and its reversibility. (2012)
  • Author(s): Liu S, Piao F, Sun X, Bai L, Peng Y, Zhong Y, Ma N, Sun W.
  • Journal Title: Neurotoxicology. Volume: 33 Pages: 1033-1039
  • DOI: DOI:10.1016/j. neuro.2012.04.020
  • Peer Reviewed
• [Journal Article] Nitrative DNA damage and Oct3/4 expression in urinary bladder cancer with Schistosomahaematobium infection. (2011)
  • Author(s): Ma N, Thanan R, Kobayashi H, Hammam O, Wishahi M, Leithy TE, Hiraku Y, Amro EK, Oikawa S, Ohnishi S, Murata M, Kawanishi S.
  • Journal Title: Biochem Biophys Res Commun. Volume: 414(2) Pages: 344-349
  • DOI: DOI:10.1016/j.bbrc.2011.09.073.
  • Peer Reviewed
• [Journal Article] Nitrative and oxidative DNA damage caused by K-ras mutation in mice. (2011)
  • Author(s): Ohnishi S, Saito H, Suzuki N, Ma N, Hiraku Y, Murata M, Kawanishi S.
  • Journal Title: Biochem Biophys Res Commun. Volume: 23 Pages: 413(2):236-240
  • DOI: DOI:10.1016/j.bbrc.2011.08.076
  • Peer Reviewed
• [Journal Article] Localization of D-serine and serine racemase in neurons and neuroglias in mouse brain. (2011)
  • Author(s): Ding X, Ma N, Nagahama M, Yamada K, Semba R.
  • Journal Title: Neurol Sci. Volume: 32(2) Pages: 263-267
  • DOI: DOI:10.1007/s10072-010-0422-2.
  • Peer Reviewed
• [Journal Article] Distribution of D-aspartate- immunopositive cells in the ganglion cell layer of adult rat retina. (2011)
  • Author(s): Sasoh M, Ma N, Matsubara H, Matsunaga K, Uji Y.
  • Journal Title: Ophthalmic Res. Volume: 46(1) Pages: 13-18
  • DOI: DOI:10.1159/000321944.
  • Peer Reviewed
• [Journal Article] The inflammatory changes of adipose tissue in late pregnant mice. (2011)
  • Author(s): Zhang L, Sugiyama T, Murabayashi N, Umekawa T, Ma N, Kamimoto Y, Ogawa Y, Sagawa N.
  • Journal Title: J Mol Endocrinol. Volume: 30 Pages: 47(2):157-165
  • DOI: DOI:10.1530/JME-11-0030.
  • Peer Reviewed
• [Journal Article] Nitrative and oxidative DNA damage as potential survival biomarkers for nasopharyngeal carcinoma (2011)
  • Author(s): Huang Y, Zhang B, Ma N, Murata M, Tang A, Huang G.
  • Journal Title: Medical Oncology Volume: 28(1) Pages: 377-384
  • DOI: DOI:10.1007/s12032-010-9434-2.
  • Peer Reviewed
• [Journal Article] Protection effect of taurine on nitrosative stress in the mice brain with chronic exposure to arsenic. (2010)
  • Author(s): Ma N, Sasoh M, Kawanishi S, Sugiura H, Piao F.
  • Journal Title: Journal of Biological Science. Volume: 17 Pages: S1-7
  • DOI: DOI:10.1016/j.bbrc.2011.09.073.
  • Peer Reviewed
• [Journal Article] TFPI-2 is a putative tumor suppressor gene frequently inactivated by promoter hypermethylation in nasopharyngeal carcinoma. (2010)
  • Author(s): Wang S, Xiao X, Zhou X, Huang T, Du C, YuN, Mo Y, Lin L, Zhang J, Ma N, Murata M,Huang G, Zhang Z.
  • Journal Title: BMC Cancer. Volume: 10 Pages: 617
  • DOI: DOI:10.1186/1471-2407-10-617.
  • Peer Reviewed
• [Journal Article] Thioredoxin suppresses airway inflammation independently of systemic Th1/Th2 immune modulation. (2010)
  • Author(s): Torii M, Wang L, Ma N, Saito K, Hori T, Sato-Ueshima M, Koyama Y, Nishikawa H, Katayama N, Mizoguchi A, Shiku H, Yodoi J,Kuribayashi K, Kato T.
  • Journal Title: European Journal of Immunology. Volume: 40(3) Pages: 787-796
  • DOI: DOI:10.1002/eji.200939724.
  • Peer Reviewed
• [Journal Article] Transgenic mice overproducing human thioredoxin-1, an antioxidative and anti-apoptotic protein, prevents diabetic embryopathy. (2010)
  • Author(s): Kamimoto Y, Sugiyama T, Kihira T, Murabayashi N, Umekawa T, Nagao K, Ma N, Toyoda N, Yodoi J, Sagawa N.
  • Journal Title: Diabetologia. Volume: 53 (9) Pages: 2046-2055
  • DOI: DOI:10.1007/s00125-010-1784-y.
  • Peer Reviewed
• [Journal Article] UV irradiation after immunization induces type 1 regulatory T cells that suppress Th2-type immune responses via secretion of IL-10. (2010)
  • Author(s): Wang L, Saito K, Toda M, Hori T, Torii M, Ma N, Katayama N, Shiku H, Kuribayashi K, Kato T.
  • Journal Title: Immunobiology. Volume: 215(2) Pages: 124-132
  • DOI: DOI:10.1016/j.imbio.2009.01.013
  • Peer Reviewed
• [Journal Article] Effect of all-trans-retinoic acid on the development of chronic hypoxia-induced pulmonary hypertension. (2010)
  • Author(s): Zhang E, Jiang B, Yokochi A, Maruyama J, Mitani Y, Ma N, Maruyama K.
  • Journal Title: Circulation Journal. Volume: 74(8) Pages: 1696-1703
  • DOI: DOI:10.1253/circj.CJ-10-0097.
  • Peer Reviewed
• [Presentation] ヒト皮膚細胞におけるヒ素曝露によるCD44v6発現誘導と腫瘍形成. (2013)
  • Author(s): 大西志保、馬寧、黄世文、郭松超、郭菲〓、村田真理子、川西正祐
  • Organizer: 第83回日本衛生学会学術総会
  • Place of Presentation: 金沢
  • Year and Date: 20130324-26
• [Presentation] 多層カーボンナノチューブによる細胞内ニトロ化DNA損傷:酸化DNA損傷との比較. (2013)
  • Author(s): FeiyeGuo、馬寧、川西正祐、村田真理子、平工雄介
  • Organizer: 第83回日本衛生学会学術総会
  • Place of Presentation: 金沢
  • Year and Date: 20130324-26
• [Presentation] ラットのエストロゲン依存性放射線誘発乳癌におけるニトロ化DNA損傷と幹細胞マーカー. (2012)
  • Author(s): 大西志保、馬寧、小野田真、村田真理子、川西正祐
  • Organizer: 日本環境変異原学会第41回大会JEMS2012
  • Place of Presentation: 静岡市
  • Year and Date: 20121129-30
• [Presentation] 上咽頭癌におけるmicroRNAの調節異常の検討. (2012)
  • Author(s): 王淑民、莫穎禧、翠川薫、張哲、黄光武、馬寧、平工雄介、及川伸二、村田真理子
  • Organizer: 日本環境変異原学会第41回大会JEMS2012
  • Place of Presentation: 静岡市
  • Year and Date: 20121129-30
• [Presentation] ヒト肺における石綿線維量と酸化・ニトロ化DNA損傷との関係. (2012)
  • Author(s): 平工雄介、馬寧、川西正祐、村田真理子
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌市
  • Year and Date: 20120919-21
• [Presentation] 線維長の異なる多層カーボンナノチュープによる細胞内DNA損傷. (2012)
  • Author(s): FeiyeGuo、馬寧、川西正祐、村田真理子、平工雄介
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌市
  • Year and Date: 20120919-21
• [Presentation] プロトンボンプ阻害剤によるMn-SOD発現上昇を介したバレット食道DNA病変の抑制. (2012)
  • Author(s): タナンレイヌー、馬寧、平工雄介、及川伸二、村田真理子、川西正祐
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌市
  • Year and Date: 20120919-21
• [Presentation] 放射線によるエストロゲン依存性乳癌誘発ラットにおけるニトロ化DNA損傷と癌幹細胞マーカー. (2012)
  • Author(s): 大西志保、馬寧、小野田真、村田真理子、川西正祐
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌市
  • Year and Date: 20120919-21
• [Presentation] 上咽頭癌間質におけるalpha-smoothmuscleactinの発現トSDF-1との関連性. (2012)
  • Author(s): 王淑民、馬寧、川西正祐、平工雄介、及川伸二、謝螢、張哲、黄光武、村田真理子
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌市
  • Year and Date: 20120919-21
• [Presentation] Arsenic-induced nitrative DNA damage in human HaCaT leratinocytes. (2012)
  • Author(s): Ning Ma, Shiwen Huang, Feiye Guo, Qiaoying Yang, Shongchao Guo, Mariko Mariko, Shosuke Kawanishi.
  • Organizer: Seventh International Conference on the Biology, Chemistry and Therapeutic Application of Nitric Oxide
  • Place of Presentation: Edinburgh, Scotland
  • Year and Date: 20120722-26
• [Presentation] Nitrative DNA damage in human lugn epithelial cells treated with multi-walled carbon nanotube. (2012)
  • Author(s): Feiye Guo, Ning Ma, Shosuke Kawanishi, Mariko Murata, Yusuke Hiraku
  • Organizer: Seventh International Conference on the Biology, Chemistry and Therapeutic Application of Nitric Oxide
  • Place of Presentation: Edinburgh, Scotland
  • Year and Date: 20120722-26
• [Presentation] Cytosine methylation in EBV-mediated nasopharyngeal carcinoma in relation to nitrative stress. (2012)
  • Author(s): Ying Mo, Ning Ma, Shumin Wang, Zhe Zhang, Ying Xie, Guangwu Huang, Kaoru Midorikawa, Yusuke Hiraku, Shinji Oikawa, Shosuke Kawanishi, Mariko Murata
  • Organizer: Seventh International Conference on the Biology, Chemistry and Therapeutic Application of Nitric Oxide
  • Place of Presentation: Edinburgh, Scotland
  • Year and Date: 20120722-26
• [Presentation] Effects of taurine on iNOS-dependent DNA damage in heavy exercise skeletal muscel by inhibiting NF-kB signaling pathway (2012)
  • Author(s): Sugiura H, Okita S, Kato T, Naka T, Kawanishi S, Oshida Y, Ma N
  • Organizer: 18th Intenational Taurine Meeting
  • Place of Presentation: モロッコ国マラケシュ市
  • Year and Date: 20120409-13
• [Presentation] Parasite infection induces oxidative/nitrative DNA damage in stem-like cells in relation to carcinogenesis (2011)
  • Author(s): Raynoo Thanan, Mariko Murata, Ning Ma, Yusuke Hiraku, Shinji Oikawa, Shosuke Kawanishi
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋市
  • Year and Date: 20111003-05
• [Presentation] Nitrative DNA damage in multi-wall carbon nanotube-treated human lung epithelial cells (2011)
  • Author(s): Feiye Guo, Ning Ma, Shosuke Kawanishi, Mariko Murata, Yusuke Hiraku
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋市
  • Year and Date: 20111003-05
• [Presentation] Role of mutagenic 8-nitroguanine in estrogen- dependent radiation-induced mammary tumorigenesis of rats. (2011)
  • Author(s): Shousuke Kawanishi, N Ma, M Onoda, H Inano, S Ohnishi, M Murata
  • Organizer: 14th International Congress of Radiation Research.
  • Place of Presentation: ポーランド国ワルシャワ市
  • Year and Date: 20110828-0901
• [Presentation] 紫外線誘発皮膚癌のモデルマウスにおける8-ニトログアニン生成 (2011)
  • Author(s): 馬寧、大西志保、平工雄介、錦織千佳子、川西正祐
  • Organizer: 第33回日本光医学・光生物学会
  • Place of Presentation: 大阪
  • Year and Date: 20110722-23
• [Presentation] ヒト肺上皮細胞における多層カーボンナノチューブによる8-ニトログアニン生成. (2011)
  • Author(s): 郭霏〓、馬寧、川西正祐、村田真理子、平工雄介
  • Organizer: 第81回日本衛生学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 20110325-28
• [Presentation] ヒト肺上皮細胞におけるカーボンブラックによる8-ニトログアニン生成. (2011)
  • Author(s): 西川嘉広、馬寧、川西正祐、村田真理子、平工雄介
  • Organizer: 第81回日本衛生学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 20110325-28
• [Presentation] ヒト肺組織における石綿線維量とDNA損傷との関係. (2011)
  • Author(s): 平工雄介、酒井潔、柴田英治、上島通浩、久永直見、馬寧、川西正祐、村田真理子
  • Organizer: 第82回日本衛生学会学術総会
  • Place of Presentation: 京都
  • Year and Date: 20110324-26
• [Presentation] 癌抑制機能を有するRRAD遺伝子の上咽頭癌におけるメチル化異常. (2011)
  • Author(s): 莫頴橲、翠川薫、張哲、黄光武、馬寧、平工雄介、及川伸二、村田真理子
  • Organizer: 第82回日本衛生学会学術総会
  • Place of Presentation: 京都
  • Year and Date: 20110324-26
• [Presentation] 多層カーボンナノチューブによる細胞内ニトロ化DNA損傷:線維長との関連. (2011)
  • Author(s): グオフェイイェ、馬寧、川西正祐、村田真理子、平工雄介
  • Organizer: 第82回日本衛生学会学術総会
  • Place of Presentation: 京都
  • Year and Date: 20110324-26
• [Presentation] Nitrative DNA damage induced by multi-wall carbon nanotube in human lung epithelial cells. (2010)
  • Author(s): Feiye Guo, Ning Ma, Shosuke Kawanishi,Mariko Murata, Yusuke Hiraku
  • Organizer: 第39回日本環境変異原学会
  • Place of Presentation: つくば市
  • Year and Date: 20101116-17
• [Presentation] Nitrative DNA damage induced by carbon black in human lung epithelial cells. (2010)
  • Author(s): Yoshihiro Nishikawa, Ning Ma, Shosuke Kawanishi, Mariko Murata, Yusuke Hiraku
  • Organizer: 第39回日本環境変異原学会
  • Place of Presentation: つくば市
  • Year and Date: 20101116-17
• [Presentation] ナノ素材によるDNA損傷:カーボンブラック処理細胞における8-ニトログアニンの生成 (2010)
  • Author(s): 平工雄介,馬寧、川西正祐、村田真理子
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 20100922-24
• [Book] 8-Nitroguanine: a potential biomarker to evaluate the risk of inflammation- related carcinogenesis. (2012)
  • Author(s): Ma N, Murata M, Ohnishi S, Thanan R, Hiraku Y, Kawanishi S
  • Total Pages: 201-224
  • Publisher: Biomarker.(Editor: Tapan Khan. INTECH Publisher