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大鼠肝脏组分对二甲基亚硝胺和苯甲基亚硝胺氧化过程中几种去甲基酶的证据。

Evidence for several demethylase enzymes in the oxidation of dimethylnitrosamine and phenylmethylnitrosamine by rat liver fractions.

作者信息

Kroeger-Koepke M B, Michejda C J

出版信息

Cancer Res. 1979 May;39(5):1587-91.

PMID:34478
Abstract

The steady state kinetics and isotope effects were examined for demethylation of dimethylnitrosamine and phenylmethylnitrosamine, as well as their deuterated analogs, using the S-9 fraction, the microsomal pellet, and postmicrosomal supernatant from rat livers. The isotope effect (ratio of maximal rates for the deuterated and light substrates) using the S-9 from Long-Evans rat livers was found to be 1.82 for dimethylnitrosamine and 5.38 for phenylmethylnitrosamine. Phenobarbital was shown to induce dimethylnitrosamine demethylase activity in the microsomal pellet of both Long-Evans and Sprague-Dawley rats but to repress this activity in the postmicrosomal supernatant in the Long-Evans rats, while markedly increasing it in the Sprague-Dawley rats. It was also found that there was nitrosamine demethylase activity in the so-called "pH 5 enzymes" and in the supernatant from that preparation. The latter activity shows substantially different characteristics from that found in the other fractions.

摘要

利用大鼠肝脏的S-9组分、微粒体沉淀和微粒体后上清液,研究了二甲基亚硝胺和苯甲基亚硝胺及其氘代类似物的去甲基化的稳态动力学和同位素效应。发现使用来自Long-Evans大鼠肝脏的S-9时,二甲基亚硝胺的同位素效应(氘代底物与轻底物的最大速率之比)为1.82,苯甲基亚硝胺为5.38。苯巴比妥被证明可诱导Long-Evans大鼠和Sprague-Dawley大鼠微粒体沉淀中的二甲基亚硝胺去甲基酶活性,但在Long-Evans大鼠的微粒体后上清液中抑制该活性,而在Sprague-Dawley大鼠中则显著增加该活性。还发现所谓的“pH 5酶”及其制备的上清液中存在亚硝胺去甲基酶活性。后者的活性与在其他组分中发现的活性具有显著不同的特征。

相似文献

1
Evidence for several demethylase enzymes in the oxidation of dimethylnitrosamine and phenylmethylnitrosamine by rat liver fractions.大鼠肝脏组分对二甲基亚硝胺和苯甲基亚硝胺氧化过程中几种去甲基酶的证据。
Cancer Res. 1979 May;39(5):1587-91.
2
Kinetic studies on the hepatic microsomal metabolism of dimethylnitrosamine, diethylnitrosamine, and methylethylnitrosamine in the rat.大鼠肝脏微粒体对二甲基亚硝胺、二乙基亚硝胺和甲基乙基亚硝胺代谢的动力学研究。
J Natl Cancer Inst. 1978 Aug;61(2):517-21.
3
Further studies on the metabolism of dimethylnitrosamine by rat liver in vitro [proceedings].大鼠肝脏体外对二甲基亚硝胺代谢的进一步研究[会议论文集]
Biochem Soc Trans. 1977;5(4):1013-5. doi: 10.1042/bst0051013.
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Age course and inducibility of dimethylnitrosamine N-demethylation in rat liver.大鼠肝脏中二甲基亚硝胺N-去甲基化的年龄进程及诱导性
Acta Biol Med Ger. 1982;41(7-8):675-87.
5
Dimethylnitrosamine-demethylase: absence of increased enzyme catabolism and multiplicity of effector sites in repression. Hemoprotein involvement.二甲基亚硝胺脱甲基酶:酶分解代谢未增加及阻遏中效应位点的多样性。含血红素蛋白的参与。
Chem Biol Interact. 1976 May;13(2):127-40. doi: 10.1016/0009-2797(76)90002-8.
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Studies on the in vitro metabolism of dimethylnitrosamine by rat liver.大鼠肝脏对二甲基亚硝胺的体外代谢研究。
Toxicology. 1976 Mar;5(3):297-309. doi: 10.1016/0300-483x(76)90049-4.
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Factors affecting metabolism and mutagenicity of dimethylnitrosamine and diethylnitrosamine.影响二甲基亚硝胺和二乙基亚硝胺代谢及致突变性的因素。
Cancer Res. 1975 Sep;35(9):2307-14.
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[Effect of HF on the hepatic metabolism of dimethylnitrosamine in the rat].[高频对大鼠二甲基亚硝胺肝脏代谢的影响]
Toxicol Eur Res. 1983 Nov;5(6):273-6.
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Effect of polychlorinated biphenyls (Aroclor 1254) on inducible and repressible microsomal N-demethylases in the mouse and rat.多氯联苯(Aroclor 1254)对小鼠和大鼠体内诱导性和可抑制性微粒体N-脱甲基酶的影响。
Cancer Res. 1975 Jun;35(6):1574-9.
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Deuterium isotope effect on denitrosation and demethylation of N-nitrosodimethylamine by rat liver microsomes.氘同位素对大鼠肝脏微粒体中N-亚硝基二甲胺脱亚硝基和脱甲基作用的影响。
Cancer Res. 1987 Jul 1;47(13):3373-7.

引用本文的文献

1
Quantitative studies on the in vitro metabolic activation of dimethylnitrosamine by rat liver postmitochondrial supernatant.大鼠肝线粒体后上清液对二甲基亚硝胺体外代谢活化的定量研究。
Environ Health Perspect. 1984 Aug;57:327-32. doi: 10.1289/ehp.8457327.
2
Histochemical localization of primary and secondary alcohol dehydrogenases in whole-body, freeze-dried sections of mice.
Histochem J. 1984 Sep;16(9):931-40. doi: 10.1007/BF01003849.
3
Deuterium isotope effects in carcinogenesis by N-nitroso compounds.N-亚硝基化合物致癌作用中的氘同位素效应。
J Cancer Res Clin Oncol. 1986;112(3):229-39. doi: 10.1007/BF00395917.