Epigenetic Assessment of Environmental Chemicals Detected in Maternal Peripheral and Cord Blood Samples
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概要
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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.
著者
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Ishii Rie
Saitama Institute Of Public Health
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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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Shiota Kunio
Laboratory Of Cellular Biochemistry Animal Resource Science/veterinary Medical Sciences Graduate Sch
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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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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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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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Izumi Shun-ichiro
Department Of Obstetrics And Gynecology School Of Medicine Keio University
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Nakazawa Hiroyuki
Department Of Analytical Chemistry Faculty Of Pharmaceutical Sciences Hoshi University
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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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