Enhanced proliferative response of hepatocytes to combined inhalation and oral exposures to N,N-dimethylformamide in male rats
スポンサーリンク
概要
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Male Wistar rats were exposed by inhalation to N,N-dimethylformamide (DMF) at 0 (control), 200 or 400 ppm (v/v) for 6 hr/day, 5 days/week and 4 weeks, and each inhalation group received DMF-formulated drinking water at 0, 800, 1,600 or 3,200 ppm (w/w) for 24 hr/day, 7 days/week and 4 weeks. Both the combined inhalation and oral exposures and the single-route exposure through inhalation or ingestion induced centrilobular hypertrophy and single-cell necrosis of hepatocytes, increased plasma levels of alanine aminotransferase (ALT), increased percentage of proliferating cell nuclear antigen (PCNA)-positive hepatocytes without glutathione-S-transferase placental form (GST-P)-positive liver foci, and increased relative liver weight. Those hepatic parameters of the DMF-induced effects were classified into hypertrophic, necrotic and proliferative responses according to the pathological characteristics of affected liver. While magnitudes of the hypertrophic and necrotic responses were linearly increased with an increase in amounts of DMF uptake in the single-route exposure groups, those dose-response relationships tended to level off in the combined-exposure groups. Saturation of the hypertrophic and necrotic responses at high dose levels might be attributed to suppression of the metabolic conversion of DMF to its toxic metabolites. Percentage of PCNA-stained hepatocytes classified as the proliferative response was increased more steeply in the combined-exposure groups than in the single-route exposure groups. It was suggested that the proliferative response of hepatocytes to the combined exposures would be greater than that which would be expected under an assumption of additivity for the component proliferative responses to the single-route exposures through inhalation and ingestion.
- 2008-08-01
著者
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Fukushima S
Japan Bioassay Research Center Japan Industrial Safety And Health Association
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Ohbayashi Hisao
Japan Bioassay Research Center, Japan Industrial Safety and Health Association
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Yamazaki Kazunori
Japan Bioassay Research Center, Japan Industrial Safety and Health Association
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Aiso Shigetoshi
Japan Bioassay Research Center, Japan Industrial Safety and Health Association
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Nagano Kasuke
Japan Bioassay Research Center, Japan Industrial Safety and Health Association
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Fukushima Shoji
Japan Bioassay Research Center, Japan Industrial Safety and Health Association
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Ohta Hisayoshi
School of Allied Health Sciences, Kitasato University
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Nagano Kasuke
Japan Bioassay Research Center Japan Industrial Safety And Health Association
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長野 嘉介
Division Of Pathology Japan Bioassay Research Center
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Nagano Kasuke
Japan Bioassay Research Center
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相磯 成敏
中災防 日本バイオアッセイ研究センター
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Yamazaki K
Japan Bioassay Research Center Japan Industrial Safety And Health Association
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Aiso Shigetoshi
Japan Bioassay Research Center Japan Industrial Safety And Health Association
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Aiso Shigetoshi
Division Of Pathology Japan Bioassay Research Center Japan Industrial Safety And Health Association
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Ohbayashi Hisao
Japan Bioassay Research Center Japan Industrial Safety And Health Association
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Ohbayashi Hisao
Japan Bioassay Laboratory Japan Industrial Safety And Health Association
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Nagano K
Japan Bioassay Research Center Japan Industrial Safety And Health Association
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Fujiwara Yushi
Department Of Gastroenterological Surgery Osaka City University Graduate School Of Medicine
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Fukushima Shoji
Japan Bioassay Research Center Japan Industrial Safety And Health Association
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Fukushima Shoji
中央労働災害防止協会日本バイオアッセイ研究センター
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Ohbayashi Hisao
中央労働災害防止協会日本バイオアッセイ研究センター
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Yamazaki Kazunori
Japan Bioassay Research Center Japan Industrial Safety And Health Association
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Fukushima Shoji
Japan Bioassay Research Center
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相磯 成敏
Division Of Pathology Japan Bioassay Research Center
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長野 嘉介
Japan Bioassay Research Center Japan Industrial Safety And Health Association
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Yamazaki Kazunori
Occupational Health Res. And Dev. Center Japan Industrial Safety And Health Assoc.
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Fukushima Shoji
Japan Bioassay Res. Center Japan Industrial Safety And Health Assoc.
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Aiso Shigetoshi
Japan Bioassay Res. Center Japan Industrial Safety And Health Assoc.
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Nagano Kasuke
中央労働災害防止協会日本バイオアッセイ研究センター
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Yamazaki Kazunori
Japan Bioassay Res. Center Japan Industrial Safety And Health Assoc.
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