Metabolism of 2, 4-Dinitrotoluene, 2, 4-Dinitrobenzyl Alcohol and 2, 4-Dinitrobenzaldehyde by Rat Liver Microsomal and Cytosol Fractions(Environmental)
スポンサーリンク
概要
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The metabolism of 2, 4-dinitrotoluene (2, 4-DNT), 2, 4-dinitrobenzyl alcohol (2, 4-DNB) and 2, 4-dinitrobenzaldehyde (2, 4-DNAl) in rat liver microsomal and cytosol fractions was investigated. The objectives of these studies were to determine whether 2, 4-DNAl, a potent mutagen, is produced in the oxidation of 2, 4-DNB to 2, 4-DNBA and to clarify the nature of the enzymes responsible for the oxidation of 2, 4-DNT to 2, 4-DNB, 2, 4-DNAl and 2, 4-dinitrobenzoic acid (2, 4-DNBA). Data obtained from high-performance liquid chromatography indicated that the major products of 2, 4-DNT, 2, 4-DNB and 2, 4-DNAl in the microsomal and cytosol preparations were 2, 4-DNB, 2, 4-DNAl, and 2, 4-DNBA and 2, 4-DNB, respectively. The results indicate that 2, 4-DNAl is an intermediate in the oxidation of 2, 4-DNB to 2, 4-DNBA. In addition, data obtained by incubating 2, 4-DNT, 2, 4-DNB or 2, 4-DNAl with microsomal or cytosol fraction under air, nitrogen and various concentrations of CO in oxygen, using cofactors nicotinamide adenine dinucleotide phosphate and reduced nicotinamide adenine dinucleotide phosphate [NAD (P) and NAD (P) H] and inhibitors (SKF-525A, dimethyl sulfoxide, chloral hydrate, allopurinol, pyrazole and o-phenanthroline) suggest that : (a) oxidation of 2, 4-DNT to 2, 4-DNB is mediated by microsomal P-450 ; (b) oxidation of 2, 4-DNB to 2, 4-DNAl is mediated mainly by cytochrome P-450 and NAD-dependent alcohol dehydrogenase ; (c) oxidation of 2, 4-DNAl to 2, 4-DNBA and reduction of 2, 4-DNAl to 2, 4-DNB may be mediated by NAD( P)-dependent aldehyde dehydrogenases and NAD (P) H-dependent aldehyde reductases, respectively. These results indicate that 2, 4-DNT is metabolized stepwise to 2, 4-DNB, 2, 4-DNAl and 2, 4-DNBA in the rat liver and suggest that the oxidation of 2, 4-DNB to 2, 4-DNAl is a metabolic activation of 2, 4-DNT and that the microsomal cytochrome P-450 and alcohol dehydrogenase may play an important role in the metabolic activation of 2, 4-DNT.
- 社団法人日本薬学会の論文
- 1987-04-25
著者
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宮原 龍郎
富山医科薬科大学薬学部毒性学
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宮原 龍郎
Faculty of pharmaceutical science, Toyama Medical and Pharmaceutical University
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森 正明
Faculty Of Pharmaceutical Sciences Toyama Medical And Pharmaceutical University
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狐塚 寛
Faculty of Pharmaceutical Sciences, Toyama University
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本田 昂
School Of Medicine
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森 佳洋
Faculty Of Pharmaceutical Sciences Toyama Medical And Pharmaceutical University
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川尻 忠司
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University
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佐山 三千雄
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University
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庄司 美樹
Radioisoiope Laboratory, Toyama Medical and Pharmaceutical University
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本田 [たかし]
School of Medicine, Toyama Medical and Pharmaceutical University
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狐塚 寛
富山医科薬科大学薬学部
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宮原 竜郎
富山医科薬科大学 薬
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狐塚 寛
富山大学薬学部
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宮原 龍郎
富山医科薬科大学薬学部
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佐山 三千雄
Faculty Of Pharmaceutical Sciences Toyama Medical And Pharmaceutical University
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庄司 美樹
Radioisoiope Laboratory Toyama Medical And Pharmaceutical University
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川尻 忠司
Faculty Of Pharmaceutical Sciences Toyama Medical And Pharmaceutical University
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