Epigenetic Assessment of Environmental Chemicals Detected in Maternal Peripheral and Cord Blood Samples
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概要
- 論文の詳細を見る
Epigenetic alteration is an emerging paradigm underlying the long-term effects of chemicals on gene functions. Various chemicals, including organophosphate insecticides and heavy metals, have been detected in the human fetal environment. Epigenetics by DNA methylation and histone modifications, through dynamic chromatin remodeling, is a mechanism for genome stability and gene functions. To investigate whether such environmental chemicals may cause epigenetic alterations, we studied the effects of selected chemicals on morphological changes in heterochromatin and DNA methylation status in mouse ES cells (ESCs). Twenty-five chemicals, including organophosphate insecticides, heavy metals and their metabolites, were assessed for their effect on the epigenetic status of mouse ESCs by monitoring heterochromatin stained with 4¢,6-diamino-2-phenylindole (DAPI). The cells were surveyed after 48 or 96 h of exposure to the chemicals at the serum concentrations of cord blood. The candidates for epigenetic mutagens were examined for the effect on DNA methylation at genic regions. Of the 25 chemicals, five chemicals (diethyl phosphate (DEP), mercury (Hg), cotinine, selenium (Se) and octachlorodipropyl ether (S-421)) caused alterations in nuclear staining, suggesting that they affected heterochromatin conditions. Hg and Se caused aberrant DNA methylation at gene loci. Furthermore, DEP at 0.1 ppb caused irreversible heterochromatin changes in ESCs, and DEP-, Hg- and S-421-exposed cells also exhibited impaired formation of the embryoid body (EB), which is an in vitro model for early embryos. We established a system for assessment of epigenetic mutagens. We identified environmental chemicals that could have effects on the human fetus epigenetic status.
- 2011-08-01
著者
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岩崎 雄介
星薬科大学薬品分析化学教室
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Makino Tsunehisa
東海大学
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Makino T
Tokai University
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斉藤 謙一
北海道薬科大学
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Ishii Rie
Saitama Institute Of Public Health
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Sugi Toshitaka
東海大学 医学部産婦人科学
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Murano T
Department Of Obstetrics And Gynecology Specialized Clinical Science Tokai University School Of Medi
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Murano Takayo
Department Of Obstetrics And Gynecology
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Iwasaki Yusuke
Deparment of Cardiology, Osaka General Medical Center
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Ito Rie
Department Of Analytical Chemistry Faculty Of Pharmaceutical Sciences Hoshi University
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Saito K
Department Of Kampo Medicinal Science Hokkaido College Of Pharmacy
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Shiota Kunio
Laboratory Of Cellular Biochemistry Animal Resource Science/veterinary Medical Sciences Graduate Sch
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Sugino N
Department Of Obstetrics And Gynecology Yamaguchi University Graduate School Of Medicine
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Kondo Fumio
Department Of Amimal Hasbandry Faculty Of Agriculture Tohoku University
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Sugino Norihiro
Department Of Obstetrics And Gynecology Graduate School Of Medicine Yamaguchi University
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Suzuki T
Department Of Obstetrics And Gynecology Tokai University School Of Medicine
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Yagi Shintaro
Laboratory Of Cellular Biochemistry Animal Resource Sciences/veterinary Medical Sciences The Univers
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HORIE Masakazu
Saitama Institute of Public Health
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Satoshi Takatori
Osaka Prefectural Institute Of Public Health
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斉藤 謙一
Department Of Physiology And Anatomy Nihon University College Of Pharmacy
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Ohgane Jun
Laboratory Of Cellular Biochemistry Animal Resource Science/veterinary Medical Sciences Graduate Sch
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Saito Koichi
Department Of Analytical Chemistry Faculty Of Pharmaceutical Sciences Hoshi University
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Hayashi Rumiko
Department Of Chemical System Engineering Graduate School Of Engineering The University Of Tokyo
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Nakazawa H
Department Of Analytical Chemistry Faculty Of Pharmaceutical Sciences Hoshi University
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Izumi Shun-ichiro
Department Of Obstetrics And Gynecology School Of Medicine Keio University
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Izumi S
Tokai Univ. School Of Medicine
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Makino Tsunehisa
Department Of Obstetrics And Gynecology Center For Specialized Clinical Science Tokai University Sch
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Saguchi Ken-ichi
Laboratory Of Biopharmaceutics School Of Pharmaceutical Sciences Showa University
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Shinozaki Kazuo
Riken Kanagawa Jpn
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Sasaki Kanako
Riken Kanagawa Jpn
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Murano Takayo
Department Of Obstetrics And Gynecology Center For Specialized Clinical Science Tokai University Sch
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Izumi Shunichiro
Obstetrics And Gynecology Tokai University School Of Medicine
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ARAI Yoshikazu
Laboratory of Cellular Biochemistry, Animal Resource Sciences/Veterinary Medical Sciences, The Unive
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AKUTSU Kazuhiko
Division of Food Chemistry, Osaka Prefectural Institute of Public Health, Osaka 537-0025, Japan
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TAKATORI Satoshi
Division of Food Chemistry, Osaka Prefectural Institute of Public Health, Osaka 537-0025, Japan
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MAKINO Tsunehisa
Toubu Hospital, Shizuoka 412-0041, Japan
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Izumi Shun-ichiro
Obstetrics And Gynecology Tokai University School Of Medicine
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Makino Tsunehisa
Department Of Obstetrics And Gynecology
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Nakazawa Hiroyuki
Department Of Analytical Chemistry Faculty Of Pharmaceutical Science Hoshi University
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Saito Ken-ichi
Department Of Toxicology And Pharmacology Faculty Of Pharmaceutical Sciences The University Of Tokyo
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Akutsu Kazuhiko
Division Of Food Chemistry Osaka Prefectural Institute Of Public Health
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Izumi S
Department Of Obstetrics And Gynecology School Of Medicine Tokai University
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Yagi Shintaro
Laboratory Of Cellular Biochemistry Animal Resource Sciences/veterinary Medical Sciences The Univers
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Sakoda K
Department Of Analytical Chemistry Faculty Of Pharmaceutical Sciences Hoshi University
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Makino Tsunehisa
Toubu Hospital
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Ishii R
Saitama Institute Of Public Health
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Saito Koichi
Department Of Agricultural Chemistry Faculty Of Agriculture Kyoto Prefectural University
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Kondo Fumio
Department Of Pharmacology School Of Medicine Aichi Medical University
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Arai Yoshikazu
Laboratory Of Cellular Biochemistry Animal Resource Sciences/veterinary Medical Sciences The Univers
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Arai Yoshikazu
Laboratory Of Cellular Biochemistry Animal Resource Sciences/veterinary Medical Sciences The Univers
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Makino Tsunehisa
Department Of Obstetrics & Gynecology School Of Medicine Tokai University
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Ohgane Jun
Laboratory Of Cellular Biochemistry Animal Resource Sciences/veterinary Medical Sciences The Univers
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Hayashi Rumiko
Department Of Toxicology Aichi Prefectural Institute Of Public Health
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Sakui Norihiro
Department Of Obstetrics And Gynecology Yamaguchi University Graduate School Of Medicine
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Izumi Shun-ichiro
Department Of Obstetrics And Gynecology
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Takatori Satoshi
Division of Food Chemistry, Osaka Prefectural Institute of Public Health
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SHIOTA Kunio
Laboratories of Cellular Biochemistry
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岩崎 雄介
星薬科大学薬学部薬品分析化学教室
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