An association between oxidative stress and DNA damage caused by prenatal exposure to environmental chemicals and physical growth, and allergic diseases and infections in childhood

• Project/Area Number: 25460788
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hygiene and public health
• Research Institution: Hokkaido University
• Principal Investigator: SASAKI Seiko 北海道大学, 医学(系)研究科(研究院), 助教 (30448831)
• Co-Investigator(Kenkyū-buntansha): MIYASHITA Chihiro 北海道大学, 環境健康科学研究教育センター, 特任准教授 (70632389)
• Co-Investigator(Renkei-kenkyūsha): KISHI Reiko 北海道大学, 環境健康科学研究教育センター, 特別招聘教授 (80112449) ; TAMAKOSHI Akiko 北海道大学, 大学院医学研究科, 教授 (90236737)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 環境化学物質 / DNA損傷 / 遺伝環境交互作用 / 胎児発育 / 生後発育 / 小児アレルギー性疾患・感染症 / 酸化ストレス / 胎児期曝露 / 小児アレルギー / 小児発育 / 母子保健

Outline of Final Research Achievements

We investigated adverse effects between 8-OHdG levels in maternal serum as a biomarker for DNA damage and both maternal and infant PON1, OGG1, ERCC1 and XRCC1 gene polymorphisms on physical growth, and allergic diseases and infections in childhood.
We observed an increased risk of wheeze among children aged 3.5 years carrying the ERCC1 CC genotype (aOR=2.26, 95% CI=1.03-4.95) and XRCC1 AG/AA genotype (aOR=1.94, 95% CI=0.98-3.86) with 2.7-fold increase in 8-OHdG levels. However no significant interaction of 8-OHdG levels and genotypes on allergic diseases and infections was found among children at 1.5 or 7 years of age as well as childhood physical growth.

Research Products

• [Journal Article] The Relationship between the Second-to-Fourth Digit Ratio and Behavioral Sexual Dimorphism in School-Aged Children. (2016)
  • Author(s): Mitsui T, Araki A, Miyashita C, Ito S, Ikeno T, Sasaki S, Kitta T, Moriya K, Cho K, Morioka K, Kishi R, Shinohara N, Takeda M, Nonomura K.
  • Journal Title: PLoS One. Volume: 11(1) Issue: 1 Pages: e0146849-e0146849
  • DOI: 10.1371/journal.pone.0146849
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Prenatal exposure to perfluorinated chemicals and neurodevelopment in early infancy: The Hokkaido Study (2016)
  • Author(s): H. Goudarzi, S. Nakajima, T. Ikeno, S. Sasaki, S. Kobayashi, C. Miyashita, S. Ito, A. Araki, H. Nakazawa and R. Kishi
  • Journal Title: Sci Total Environ Volume: 541 Pages: 1002-1010
  • DOI: 10.1016/j.scitotenv.2015.10.017
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effects of in utero exposure to polychlorinated biphenyls, methylmercury, and polyunsaturated fatty acids on birth size (2015)
  • Author(s): C. Miyashita, S. Sasaki, T. Ikeno, A. Araki, S. Ito, J. Kajiwara, T. Todaka, N. Hachiya, A. Yasutake, K. Murata, T. Nakajima and R. Kishi
  • Journal Title: Sci Total Environ Volume: 533 Pages: 256-265
  • DOI: 10.1016/j.scitotenv.2015.06.108
  • Peer Reviewed / Open Access
• [Journal Article] The Association of Prenatal Exposure to Perfluorinated Chemicals with Maternal Fatty Acids during Pregnancy and the Birth Weight of their Offspring:The Hokkaido Study (2015)
  • Author(s): Reiko Kishi, Tamie Nakajima, Houman Goudarzi, Sachiko Kobayashi, Seiko Sasaki, Emiko Okada, Chihiro Miyashita, Sachiko Itoh, Atsuko Araki, Tamiko Ikeno, Yusuke Iwasaki, and Hiroyuki Nakazawa
  • Journal Title: Environmental Health Perspective Volume: 印刷中 Issue: 10 Pages: 1038-1045
  • DOI: 10.1289/ehp.1408834
  • Peer Reviewed / Open Access
• [Journal Article] 喫煙，受動喫煙による児への影響(遺伝的ハイリスク群を含む) (2015)
  • Author(s): 佐々木成子, 小林澄貴, 岸玲子.
  • Journal Title: 公衆衛生. Volume: 79 Pages: 637-643
• [Journal Article] Prenatal maternal blood triglyceride and fatty acid levels in relation to exposure to di(2-ethylhexyl)phthalate: a cross-sectional study. (2015)
  • Author(s): Jia X, Harada Y, Tagawa M, Naito H, Hayashi Y, Yetti H, Kato M, Sasaki S, Araki A, Miyashita C, Ikeno T, Kishi R, Nakajima T.
  • Journal Title: Environ Health Prev Med. Volume: In press Issue: 3 Pages: 168-178
  • DOI: 10.1007/s12199-014-0440-4
  • NAID: 210000000370
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 胎児期の母の受動喫煙と児の出生体重に関する最近の研究動向. (2015)
  • Author(s): 小林澄貴, 荒木敦子, 佐々木成子, 池野多美子, 宮下ちひろ, 伊藤佐智子, 岸玲子.
  • Journal Title: 北海道公衆衛生学雑誌. Volume: 28(2) Pages: 37-48
  • NAID: 120005600756
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Demographic, behavioral, dietary and socioeconomic characteristics related to persistent organic pollutants and mercury levels in pregnant woman in Japan (2015)
  • Author(s): Miyashita C., Sasaki S., Saijo Y., Okada E., Kobayashi S., Baba T., Kajiwara J., Todaka T., Iwasaki Y., Nakazawa H., Hachiya N., Yasutake A., Murata K., Kishi R.
  • Journal Title: Chemosphere Volume: 133 Pages: 13-21
  • DOI: 10.1016/j.chemosphere.2015.02.062
  • Peer Reviewed / Open Access
• [Journal Article] Effects of prenatal Leydig cell function on the ratio of the second to fourth digit lengths in school-aged children (2015)
  • Author(s): Mitsui T., Araki A., Imai A, Sato S., Miyashita C., Ito S., Sasaki S., Kitta T., Moriya K. Cho K., Morioka K., Kihsi R., Nonomura K
  • Journal Title: PLOS One Volume: 10(3) Issue: 3 Pages: e0120636-e0120636
  • DOI: 10.1371/journal.pone.0120636
  • NAID: 120005606031
  • Peer Reviewed / Open Access
• [Journal Article] Association of maternal whole blood fatty acid status during the prenatal period with term birth dimensions: a cross- sectional study (2014)
  • Author(s): Jia X., Tagawa T., Yatsuya H., Naito H., Hayashi., Husna Y., Sasaki S., Araki A., Miyashita C., Ikeno T., Kishi R., Nakajima T
  • Journal Title: J Perinat Med Volume: in press Issue: 5
  • DOI: 10.1515/jpm-2014-0277
  • Peer Reviewed
• [Journal Article] Association between maternal exposure to di(2-ethylhexyl) phthalate and reproductive hormone levels in fetal blood: The Hokkaido Study on Environment and Children's Health (2014)
  • Author(s): Araki A., Mitsui T., Miyashita C., Nakajima T., Naito H., Ito S., Sasaki S., Cho K., Ikeno T., Nonomura K., Kishi R.
  • Journal Title: PLOS One Volume: 9(10) Issue: 10 Pages: e109039-e109039
  • DOI: 10.1371/journal.pone.0109039
  • NAID: 120005476155
  • Peer Reviewed / Open Access
• [Journal Article] Prenatal exposure to perfluoroalkyl acids and allergic diseases in earlychildhood. (2014)
  • Author(s): Okada E, Sasaki S, Kashino I, Matsuura H, Miyashita C, Kobayashi S, Itoh K, Ikeno T, Tamakoshi A, Kishi R.
  • Journal Title: Environment International Volume: 65 Pages: 127-134
  • DOI: 10.1016/j.envint.2014.01.007
  • Peer Reviewed / Open Access
• [Journal Article] Association between maternal antenatal depression and infant development: a hospital-based prospective cohort study (2014)
  • Author(s): Otake Y, Nakajima S, Uno A, Kato S, Sasaki S, Yoshioka E, Ikeno T, Kishi R
  • Journal Title: Environment Health Preventive Medicine Volume: 19(1) Issue: 1 Pages: 30-45
  • DOI: 10.1007/s12199-013-0353-7
  • NAID: 210000000292
  • Peer Reviewed / Open Access
• [Journal Article] Temporal trends of perfiuoroalkyl acids in plasma samples of pregnant women in Hokkaido, Japan, 2003-2011. (2014)
  • Author(s): Okada E, Kashino I, Matsuura H, Sasaki S, Miyashita C, Yamamoto J, Ikeno T, Ito Y, Matsumura T, Yamakoshi A, Kishi R.
  • Journal Title: Environment International Volume: 60 Pages: 89-96
  • DOI: 10.1016/j.envint.2013.07.013
  • Peer Reviewed
• [Journal Article] Ten years of progress in the Hokkaido birth cohort study on environment and children's health: cohort profile--updated 2013. (2013)
  • Author(s): Kishi R, Kobayashi S, Ikeno T, Araki A, Miyashita C, Itoh S, Sasaki S, Okada E, Kobayashi S, Kashino I, Itoh K, Nakajima S.
  • Journal Title: Environ Health Prev Med. Volume: 18(6) Pages: 429-450
  • NAID: 50009002848
  • Peer Reviewed
• [Journal Article] Genetic association of aromatic hydrocarbon receptor (AHR) and cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) polymorphisms with dioxin blood concentrations among pregnant Japanese women (2013)
  • Author(s): Kobayashi S, Sata F, Sasaki S, Ban S, Miyashita C, Okada E, Limpar M, Yoshioka E, Kajiwara J, Todaka T, Saijo Y, Kishi R
  • Journal Title: Toxicology Letters Volume: 219(3) Issue: 3 Pages: 269-278
  • DOI: 10.1016/j.toxlet.2013.03.013
  • NAID: 120005295676
  • Peer Reviewed
• [Presentation] 胎児期ビスフェノールA曝露による臍帯血中のアディポカイン，出生体重，子どもの体重への影響：北海道スタディ. (2015)
  • Author(s): 湊屋街子, 佐々木成子, 荒木敦子, 宮下ちひろ, 山本潤, 松村徹, 岸玲子.
  • Organizer: 第67回北海道公衆衛生学会
  • Place of Presentation: 旭川医科大学 (北海道・旭川市)
  • Year and Date: 2015-11-21
• [Presentation] 胎児期の母と学童期の児の喫煙曝露とADHD-RSとの関連. (2015)
  • Author(s): 西原進吉, 池野多美子, 小林澄貴, 佐々木成子, 岸玲子.
  • Organizer: 第74回日本公衆衛生学会
  • Place of Presentation: 長崎ブリックホール (長崎県・長崎市)
  • Year and Date: 2015-11-04
• [Presentation] Prenatal BPA exposure and cord blood adipokines, birth weight and child growth: the Hokkaido Study of Environment and Children’s health. (2015)
  • Author(s): Minatoya M, Sasaki S, Araki A, Miyashita C, Yamamoto J, Matsumura T, Kishi R.
  • Organizer: ISEE 2015.
  • Place of Presentation: San Paulo (Brazil)
  • Year and Date: 2015-08-30
  • Int'l Joint Research
• [Presentation] Effect of maternal AHR, CYP1A1 and GSTM1 polymorphisms and dioxins on infant birth weight The Hokkaido Study. (2015)
  • Author(s): Kobayashi S, Miyashita C, Sasaki S, Araki A, Sata F, Ban S, Kajiwara J, Todaka T, Kishi R.
  • Organizer: ISEE 2015.
  • Place of Presentation: San Paulo (Brazil)
  • Year and Date: 2015-08-30
  • Int'l Joint Research
• [Presentation] 妊婦のカフェイン摂取とCYP1A2遺伝子多型による出生時体格への影響. (2015)
  • Author(s): 佐々木成子, リンパーマリコ, 佐田文宏, 小林澄貴, 岸玲子.
  • Organizer: 第85回 日本衛生学会学術総会.
  • Place of Presentation: 和歌山県民文化会館, 和歌山県, 和歌山市.
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] 臍帯血ビスフェノールAと児のIGF2DNAメチル化との関連-北海道スタディ. (2015)
  • Author(s): 小林祥子, 安住薫, 佐々木成子, 松村徹, 山本潤, 石塚真由美, 宮下ちひろ, 池野多美子, 荒木敦子, 岸玲子.
  • Organizer: 第85回 日本衛生学会学術総会.
  • Place of Presentation: 和歌山県民文化会館, 和歌山県, 和歌山市.
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] ダイオキシン類曝露と胎児発育との関連:遺伝的なリスクについて-北海道スタディ. (2015)
  • Author(s): 小林澄貴, 宮下ちひろ, 佐々木成子, 荒木敦子 佐田文宏, 坂晋, 梶原淳睦, 戸高尊, 岸玲子.
  • Organizer: 第85回 日本衛生学会学術総会.
  • Place of Presentation: 和歌山県民文化会館, 和歌山県, 和歌山市.
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] 胎児期MEHP曝露による神経行動発達への影響-北海道スタディ. (2015)
  • Author(s): 湊屋街子, 佐々木成子, 中島そのみ, 那須民江, 後藤裕子, 宮下ちひろ, 荒木敦子,小林澄貴, 池野多美子, 岸玲子.
  • Organizer: 第85回 日本衛生学会学術総会.
  • Place of Presentation: 和歌山県民文化会館, 和歌山県, 和歌山市.
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] 有機塩素系農薬への胎児期曝露による児の性ホルモン濃度への影響:北海道スタディ. (2015)
  • Author(s): 荒木敦子, 宮下ちひろ, 金澤文子, 伊藤佐智子, 三井貴彦, 佐々木成子, 水谷太, 苣木洋一, 野々村克也, 岸玲子.
  • Organizer: 第85回 日本衛生学会学術総会.
  • Place of Presentation: 和歌山県民文化会館, 和歌山県, 和歌山市.
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] 有機塩素系農薬が乳幼児の免疫に与える影響-北海道スタディ. (2015)
  • Author(s): 宮下ちひろ, 金澤文子, 佐々木成子, 池野多美子, 荒木敦子, 伊藤佐智子, 小林祥子, 水谷太, 苣木洋一, 岸玲子.
  • Organizer: 第85回 日本衛生学会学術総会.
  • Place of Presentation: 和歌山県民文化会館, 和歌山県, 和歌山市.
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] Prenatal bisphenol A exposure and birth outcomes: The Hokkaido Study. (2014)
  • Author(s): Minatoya M, Sasaki S, Nakajima S, Yamamoto J, Araki A, Itoh S, Miyashita C, Matsuura T, Nonomura K, Mitsui T, Cho K, Kishi R.
  • Organizer: 2014 Conference of International Society for Environmental Epidemiology Asia Chapter.
  • Place of Presentation: Xinhua Hospital, Shanghai, China.
  • Year and Date: 2014-11-29 – 2014-12-02
• [Presentation] Perinatal PFAAs Exposure Cause Various Health Outcomes on Offspring Including Effects on Reproductive and Thyroid Hormones: The Hokkaido Study. (2014)
  • Author(s): Kishi R, Araki A, Itoh S, Miyashita C, Goudarzi H, Kobayashi S, Sasaki S, Kashino I, Nakazawa H, Nakajima T, Mitsui T, Nonomura K.
  • Organizer: PPTOX IV.
  • Place of Presentation: Boston Marriott Long Wharf Hotel, Boston, USA.
  • Year and Date: 2014-10-26 – 2014-10-29
• [Presentation] Association between maternal exposure to di(2-ethylhexyl) phthalate and sex hormone levels in fetal blood. (2014)
  • Author(s): Araki A, Mitsui T, Miyashita C, Nakajima T, Nakazawa H, Sasaki S, Ikeno T, Cho K, Itoh S, Nonomura K, Kishi R.
  • Organizer: 26th Annual International Society for Environmental Epidemiology Conference - From Local to Global: Advancing Science for Policy in Environmental Health.
  • Place of Presentation: Husky Union Building, Seattle, USA.
  • Year and Date: 2014-08-24 – 2014-08-28
• [Presentation] Exposure to perfluoroalkyl chemicals and neurodevelopment at 6 months of age. (2014)
  • Author(s): Goudarzi H, Ikeno T, Kobayashi S, Araki A, Miyashita C, Sasaki S, Nakajima S, Nakazawa H, Kishi R.
  • Organizer: 26th Annual International Society for Environmental Epidemiology Conference - From Local to Global: Advancing Science for Policy in Environmental Health.
  • Place of Presentation: Husky Union Building, Seattle, USA.
  • Year and Date: 2014-08-24 – 2014-08-28
• [Presentation] Effect of PFOS and PFOA exposure in utero on reproductive hormones levels at birth. (2014)
  • Author(s): Itoh S, Araki A, Miyashita C, Nakazawa H, Mitsui T, Cho K, Sasaki S, Ikeno T, Nonomura K, Kishi R.
  • Organizer: 26th Annual International Society for Environmental Epidemiology Conference - From Local to Global: Advancing Science for Policy in Environmental Health.
  • Place of Presentation: Husky Union Building, Seattle, USA.
  • Year and Date: 2014-08-24 – 2014-08-28
• [Presentation] The effects of perfluoroalkyl acids (PFAAs) exposure in utero on IGF2/H19 DNA methylation in cord blood. (2014)
  • Author(s): Kobayashi S, Azumi K, Sasaki S, Ishizuka M, Nakazawa H, Okada E, Kobayashi S, Goudarzi H, Itoh S, Miyashita C, Ikeno T, Araki A, Kishi R.
  • Organizer: 26th Annual International Society for Environmental Epidemiology Conference - From Local to Global: Advancing Science for Policy in Environmental Health.
  • Place of Presentation: Husky Union Building, Seattle, USA.
  • Year and Date: 2014-08-24 – 2014-08-28
• [Presentation] 胎児期ビスフェノールA曝露による臍帯血中性ホルモン濃度への影響. (2014)
  • Author(s): 佐々木成子, 山本潤, 荒木敦子, 伊藤佐智子, 宮下ちひろ, 三井貴彦, 長和俊, 野々村克也, 松村徹, 岸玲子.
  • Organizer: 第84回 日本衛生学会学術総会.
  • Place of Presentation: 岡山コンベンションセンター, 岡山県, 岡山市
  • Year and Date: 2014-05-25 – 2014-05-27
• [Presentation] DEHPへの胎児期曝露による児の性ホルモン濃度への影響. (2014)
  • Author(s): 荒木敦子, 三井貴彦, 宮下ちひろ, 那須民江, 伊藤佐智子, 佐々木成子, 長和俊, 池野多美子, 野々村克也, 岸玲子.
  • Organizer: 第84回 日本衛生学会学術総会.
  • Place of Presentation: 岡山コンベンションセンター, 岡山県, 岡山市
  • Year and Date: 2014-05-25 – 2014-05-27
• [Presentation] PFOS. PFOAの胎児期曝露が与える児の出生時性ホルモン濃度への影響. (2014)
  • Author(s): 伊藤佐智子, 荒木敦子, 宮下ちひろ, 中澤裕之, 三井貴彦, 長和俊, 佐々木成子, 池野多美子, 野々村克也, 岸玲子.
  • Organizer: 第84回 日本衛生学会学術総会.
  • Place of Presentation: 岡山コンベンションセンター, 岡山県, 岡山市
  • Year and Date: 2014-05-25 – 2014-05-27
• [Presentation] 妊婦の受動喫煙が児の出生時体格へ及ぼす影響:遺伝的なハイリスク群について-環境と子どもの健康に関する北海道スタディ-. (2014)
  • Author(s): 小林澄貴, 佐々木成子, 佐田文宏, 宮下ちひろ, 池野多美子, 荒木敦子, 岸玲子.
  • Organizer: 北海道小児保健研究会. 平成26年度総会.
  • Place of Presentation: 札幌医科大学臨床第一講堂, 北海道,札幌市.
  • Year and Date: 2014-05-24
• [Presentation] 胎児期ビスフェノールA曝露による臍帯血中性ホルモン濃度への影響 (2014)
  • Author(s): 佐々木成子, 山本潤, 荒木敦子, 伊藤佐智子, 宮下ちひろ, 三井貴彦, 長和俊, 野々村克也, 松村徹, 岸玲子.
  • Organizer: 第84回日本衛生学会学術総会
  • Place of Presentation: 岡山コンベンションセンター, 岡山市
• [Presentation] DEHPへの胎児期曝露による児の性ホルモン濃度への影響 (2014)
  • Author(s): 荒木敦子, 三井貴彦, 宮下ちひろ, 田川雅史, 中島民江, 伊藤佐智子, 佐々木成子, 長和俊, 池野多美子,野々村克也, 岸玲子.
  • Organizer: 第84回日本衛生学会学術総会
  • Place of Presentation: 岡山コンベンションセンター, 岡山市
• [Presentation] PFOS・PFOAの胎児期曝露が与える児の出生時性ホルモン濃度への影響 (2014)
  • Author(s): 伊藤佐智子, 荒木敦子, 宮下ちひろ, 中澤裕之, 三井貴彦, 長和俊, 佐々木成子, 池野多美子, 野々村克也,岸玲子.
  • Organizer: 第84回日本衛生学会学術総会
  • Place of Presentation: 岡山コンベンションセンター, 岡山市
• [Presentation] Relationship between prenatal exposure to perfluorinated compounds and allergic diseases in infants. (2013)
  • Author(s): Okada E, Kashino I, Sasaki S, Miyashita C, Ikeno T, Araki A, Yamamoto J, Matsuura H, Matsumura T, Tamakoshi A, Kishi R.
  • Organizer: Environment and Health-Bridging South, North, East and West Conference of ISEE, ISES and ISIAQ.
  • Place of Presentation: The Congress Center Basel, Basel, Switzerland.
• [Presentation] Prenatal exposure to 11 perfluorinated compounds (PFCs) and infant weight in the Hokkaido Study on Environmental and Children’s Health. (2013)
  • Author(s): Kasino I, Okada E, Sasaki S, Miyashita C, Ikeno T, Araki A, Yamamoto J, Matsuura H, Matsumura T, Tamakoshi A, Kishi R.
  • Organizer: Environment and Health-Bridging South, North, East and West Conference of ISEE, ISES and ISIAQ.
  • Place of Presentation: The Congress Center Basel, Basel, Switzerland.
• [Presentation] The effects of hydroxylated PCBs in maternal serum on infant thyroid hormons. (2013)
  • Author(s): Itoh S, Kajiwara J, Miyashita C, Kobayashi S, Sasaki S, Ban S, Ikeno T, Araki A, Kishi R.
  • Organizer: Environment and Health-Bridging South, North, East and West Conference of ISEE, ISES and ISIAQ.
  • Place of Presentation: The Congress Center Basel, Basel, Switzerland.