Metabolism of 2,4-dinitrotoluene, 2,4-dinitrobenzyl alcohol and 2,4-dinitrobenzaldehyde by rat liver microsomal and cytosol fractions.
Metabolism of 2,4-dinitrotoluene, 2,4-dinitrobenzyl alcohol and 2,4-dinitrobenzaldehyde by rat liver microsomal and cytosol fractions.
复制标题
大鼠肝微粒体和细胞质组分对 2,4-二硝基甲苯、2,4-二硝基苯甲醇和 2,4-二硝基苯甲醛的代谢。
DOI：
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发表时间：
1987
影响因子：
1.7
通讯作者：
H. Kozuka
中科院分区：
文献类型：
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作者：
M. Shoji;M. Mori;T. Kawajiri;M. Sayama;Y. Mori;T. Miyahara;T. Honda;H. Kozuka
研究了2,4 -二硝基甲苯（2,4 - dnt）、2,4 -二硝基苄基醇（2,4 - dnb）和2,4 -二硝基苯甲醛（2,4 - dnal）在大鼠肝微粒体和细胞质组分中的代谢。这些研究的目的是确定是否在2,4 - dnb氧化为2,4 - dnba的过程中产生了2,4 - dnai，并阐明了将2,4 - dnt氧化为2,4 - dnb、2,4 - dnal和2,4 -二硝基苯甲酸（2,4 - dnba）的酶的性质。高效液相色谱分析结果表明，微粒体和细胞质制剂中2,4 - DNT、2,4 - dnb和2,4 -DNAl的主要产物分别为2,4 - dnb、2,4 -DNAl和2,4 - dnba和2,4 - dnb。结果表明2,4 - dnal是2,4 - dnb氧化为2,4 - dnba的中间体。此外，利用辅助因子烟酰胺腺嘌呤二核苷酸磷酸和还原性烟酰胺腺嘌呤二核苷酸磷酸[NAD (P)和NAD (P) H]和抑制剂（SKF-525A、二甲亚砜、水合氯醛、别嘌呤醇、吡唑和ο-菲罗啉）将2,4 - dnt、2,4 - dnb或2,4 - dnal与微粒体或细胞质组分在空气、氮气和不同浓度的氧气中孵育得到的数据表明：(a) 2,4 - dnt氧化为2,4 - dnb由微粒体P-450介导；(b) 2,4 - dnb氧化为2,4 - dnal主要由细胞色素P-450和nadd依赖性醇脱氢酶介导；(c) 2,4 - dnal氧化为2,4 - dnba和2,4 - dnal还原为2,4 - dnb可能分别由NAD (P)依赖的醛脱氢酶和NAD (P) h依赖的醛还原酶介导。这些结果表明，2,4 - dnt在大鼠肝脏中被逐步代谢为2,4 - dnb、2,4 - dnal和2,4 - dnba，表明2,4 - dnb氧化为2,4 - dnal是2,4 - dnt的代谢激活，而微体细胞色素P-450和乙醇脱氢酶可能在2,4 - dnt的代谢激活中起重要作用。
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-DNAI, 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 ο- 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.