Identification of crotonaldehyde as a hepatic microsomal metabolite formed by alpha-hydroxylation of the carcinogen N-nitrosopyrrolidine.
Identification of crotonaldehyde as a hepatic microsomal metabolite formed by alpha-hydroxylation of the carcinogen N-nitrosopyrrolidine.
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鉴定巴豆醛为致癌物 N-亚硝基吡咯烷的 α-羟基化形成的肝微粒体代谢物。
DOI：
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发表时间：
1988
影响因子：
4.1
通讯作者：
S. Hecht
中科院分区：
文献类型：
--
作者：
M. Wang;F. Chung;S. Hecht
巴豆醛（2-丁烯醛）与DNA反应，具有致突变性和致癌性，被鉴定为肝癌原N-亚硝基吡咯烷的肝微粒体代谢产物。用（2，4-二硝基苯）肼试剂衍生化来自Aroclor预处理或对照F344大鼠的N-亚硝基吡咯烷、辅因子和肝微粒体的孵育混合物，并通过高效液相色谱法分析所得混合物。巴豆醛（2，4-二硝基苯）腙在两种不同体系中的保留时间、紫外光谱和质谱图进行了鉴定。在一定的底物浓度范围内，4-羟基丁醛（先前已被鉴定为NPYR的代谢产物）与巴豆醛的比值为1.5-2。底物浓度在1 - 8 mM之间时，巴豆醛的Km和nu max近似值分别为5.8 mM和0.6 nmol/min/mg蛋白质，4-羟基丁醛的Km和nu max近似值分别为14.1 mM和1.7 nmol/min/mg蛋白质，使用Aroclor预处理大鼠的微粒体。α-乙酰氧基-N-亚硝基吡咯烷是N-亚硝基吡咯烷α-羟基化反应起始产物的稳定前体，在酯酶催化的溶剂分解反应中，4-羟基丁醛与巴豆醛的比例为1.9。这些结果表明，巴豆醛是在N-亚硝基吡咯烷的代谢α-羟基化后形成的，并表明它可能参与N-亚硝基吡咯烷-大分子相互作用。
Crotonaldehyde (2-butenal), which reacts with DNA and is mutagenic and carcinogenic, was identified as a hepatic microsomal metabolite of the hepatocarcinogen N-nitrosopyrrolidine. Incubation mixtures of N-nitrosopyrrolidine, cofactors, and hepatic microsomes from Aroclor pretreated or control F344 rats were derivatized with (2,4-dinitrophenyl)hydrazine reagent and the resulting mixtures analyzed by high-performance liquid chromatography. Crotonaldehyde (2,4-dinitrophenyl)hydrazone was identified by its retention time in two different systems and by its ultraviolet and mass spectrum. The ratio of 4-hydroxybutyraldehyde, which has previously been identified as a metabolite of NPYR, to crotonaldehyde was 1.5-2 over a range of substrate concentrations. The approximate values of Km and nu max for crotonaldehyde were 5.8 mM and 0.6 nmol/min/mg of protein and for 4-hydroxybutyraldehyde 14.1 mM and 1.7 nmol/min/mg of protein, for substrate concentrations between 1 and 8 mM, with microsomes from Aroclor pretreated rats. The ratio of 4-hydroxybutyraldehyde to crotonaldehyde was 1.9 upon esterase-catalyzed solvolysis of alpha-acetoxy-N-nitrosopyrrolidine, a stable precursor to the initial product of N-nitrosopyrrolidine alpha-hydroxylation. These results demonstrate that crotonaldehyde is formed upon metabolic alpha-hydroxylation of N-nitrosopyrrolidine and suggest that it may be involved in N-nitrosopyrrolidine-macromolecule interactions.
脱氧鸟苷与 α-乙酰氧基-N-亚硝基吡咯烷、4-(乙酯基亚硝基氨基)丁醛或巴豆醛反应形成环状 1,N2- 加合物。
影响因子：
11.2
作者：
Chung,FL;Hecht,SS
通讯作者：
Hecht,SS
影响因子：
11.2
作者：
F. Chung;F. Chung;Takuji Tanaka;S. Hecht
通讯作者：
F. Chung;F. Chung;Takuji Tanaka;S. Hecht
烟草制品中 N-亚硝胺的形成和分析及其在消费者体内的内源性形成。
DOI：
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发表时间：
1984
期刊：
IARC scientific publications
影响因子：
--
作者：
Hoffmann,D;Brunnemann,KD;Adams,JD;Hecht,SS
通讯作者：
Hecht,SS