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2-甲氧基-4-氨基偶氮苯和3-甲基胆蒽对大鼠细胞色素P-448同工酶的器官选择性诱导作用。

Organ selective induction of cytochrome P-448 isozymes in the rat by 2-methoxy-4-aminoazobenzene and 3-methylcholanthrene.

作者信息

Degawa M, Yamada H, Hishinuma T, Masuko T, Hashimoto Y

机构信息

Department of Hygienic Chemistry, Tohoku University, Miyagi.

出版信息

J Biochem. 1987 Jun;101(6):1437-45. doi: 10.1093/oxfordjournals.jbchem.a122013.

DOI:10.1093/oxfordjournals.jbchem.a122013
PMID:3312182
Abstract

Male Sprague Dawley rats were injected intraperitoneally with 2-methoxy-4-amino-azobenzene (2-MeO-AAB) or 3-methylcholanthrene (MC), and then the expression of microsomal cytochrome P-450 isozymes in liver and extrahepatic tissues was investigated by means of immunological methods and a bacterial mutation test. The results of protein A-enzyme-linked immunosorbent assaying and immunoblotting using anti-rat cytochrome P-448 monoclonal antibodies showed that MC induced at least two microsomal cytochrome P-448 isozymes, a high spin form (cytochrome P-448H) and a low spin form (cytochrome P-448L), in liver, but that it induced only cytochrome P-448L in extrahepatic tissues such as lung, kidney, small intestine, and colon. The results also indicated that, in contrast to MC, 2-MeO-AAB selectively induced microsomal cytochrome P-448H in liver but did not induce any cytochrome P-448 isozymes in extrahepatic tissues. The activities of 9,000 X g supernatants from the individual organs, as to the mutagenic conversion of 3 aromatic amines (3-amino-1-methyl-5H-pyrido(4,3-b)indole, 2-amino-6-methyldipyrido(1,2-a: 3',2'-d)-imidazole and 3-methoxy-4-aminoazobenzene), toward Salmonella typhimurium TA 98 bacteria were dependent upon the quantity and/or quality of the microsomal cytochrome P-448 isozymes in the organs.

摘要

将雄性斯普拉格-道利大鼠腹腔注射2-甲氧基-4-氨基偶氮苯(2-MeO-AAB)或3-甲基胆蒽(MC),然后通过免疫学方法和细菌突变试验研究肝脏和肝外组织中微粒体细胞色素P-450同工酶的表达。使用抗大鼠细胞色素P-448单克隆抗体进行蛋白A-酶联免疫吸附测定和免疫印迹的结果表明,MC在肝脏中诱导至少两种微粒体细胞色素P-448同工酶,一种高自旋形式(细胞色素P-448H)和一种低自旋形式(细胞色素P-448L),但在肺、肾、小肠和结肠等肝外组织中仅诱导细胞色素P-448L。结果还表明,与MC相反,2-MeO-AAB在肝脏中选择性诱导微粒体细胞色素P-448H,但在肝外组织中不诱导任何细胞色素P-448同工酶。各器官9000×g上清液对3种芳香胺(3-氨基-1-甲基-5H-吡啶并(4,3-b)吲哚、2-氨基-6-甲基二吡啶并(1,2-a:3',2'-d)-咪唑和3-甲氧基-4-氨基偶氮苯)向鼠伤寒沙门氏菌TA 98细菌的诱变转化活性取决于器官中微粒体细胞色素P-448同工酶的数量和/或质量。

相似文献

1
Organ selective induction of cytochrome P-448 isozymes in the rat by 2-methoxy-4-aminoazobenzene and 3-methylcholanthrene.2-甲氧基-4-氨基偶氮苯和3-甲基胆蒽对大鼠细胞色素P-448同工酶的器官选择性诱导作用。
J Biochem. 1987 Jun;101(6):1437-45. doi: 10.1093/oxfordjournals.jbchem.a122013.
2
Induction of cytochrome P-448 isozyme(s) in primary cultured rat hepatocytes by drugs which induce different isozymes in vivo.体内诱导不同同工酶的药物对原代培养大鼠肝细胞中细胞色素P - 448同工酶的诱导作用。
Biochem Biophys Res Commun. 1987 Nov 13;148(3):947-53. doi: 10.1016/s0006-291x(87)80224-3.
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Induction of a high spin form of microsomal cytochrome P-448 in rat liver by 4-aminoazobenzene derivatives.4-氨基偶氮苯衍生物对大鼠肝脏微粒体细胞色素P-448高自旋形式的诱导作用。
Biochem Pharmacol. 1986 Oct 15;35(20):3565-70. doi: 10.1016/0006-2952(86)90627-1.
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3-Methoxy-4-aminoazobenzene, a selective inducer for a high spin form of cytochrome P-448 in rat liver microsomes.3-甲氧基-4-氨基偶氮苯,大鼠肝微粒体中细胞色素P-448高自旋形式的选择性诱导剂。
Biochem Biophys Res Commun. 1985 Dec 31;133(3):1072-7. doi: 10.1016/0006-291x(85)91245-8.
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Species difference among experimental rodents in the activity and induction of cytochrome P-450 isozymes for mutagenic activation of carcinogenic aromatic amines.实验啮齿动物在细胞色素P - 450同工酶的活性及诱导方面的种属差异,这些同工酶参与致癌性芳香胺的诱变活化。
Jpn J Cancer Res. 1990 Dec;81(12):1253-8. doi: 10.1111/j.1349-7006.1990.tb02687.x.
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Co-induction of cytochrome P-450 isozymes in rat liver by 2,4,5,2',4',5'-hexachlorobiphenyl or 3-methoxy-4-aminoazobenzene.2,4,5,2',4',5'-六氯联苯或3-甲氧基-4-氨基偶氮苯对大鼠肝脏细胞色素P-450同工酶的共诱导作用。
Mol Pharmacol. 1987 Aug;32(1):206-11.
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3-Methoxy-4-aminoazobenzene, a unique carcinogenic aromatic amine as a substrate for cytochrome-P-450-mediated mutagenesis.
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Changes in the quantity and activity of cytochrome P-450 isozymes in primary cultured rat hepatocytes.原代培养大鼠肝细胞中细胞色素P-450同工酶的数量和活性变化
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A simple method for assessment of rat cytochrome P-448 isozymes responsible for the mutagenic activation of carcinogenic chemicals.
Mutat Res. 1988 Oct;203(5):333-8. doi: 10.1016/0165-1161(88)90029-5.
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Androgen-dependent renal microsomal cytochrome P-450 responsible for N-hydroxylation and mutagenic activation of 3-methoxy-4-aminoazobenzene in the BALB/c mouse.
Cancer Res. 1990 May 1;50(9):2729-33.

引用本文的文献

1
Oxidation of uroporphyrinogen by methylcholanthrene-induced cytochrome P-450. Essential role of cytochrome P-450d.甲基胆蒽诱导的细胞色素P-450对尿卟啉原的氧化作用。细胞色素P-450d的重要作用。
Biochem J. 1989 Feb 15;258(1):247-53. doi: 10.1042/bj2580247.
2
Species difference among experimental rodents in the activity and induction of cytochrome P-450 isozymes for mutagenic activation of carcinogenic aromatic amines.实验啮齿动物在细胞色素P - 450同工酶的活性及诱导方面的种属差异,这些同工酶参与致癌性芳香胺的诱变活化。
Jpn J Cancer Res. 1990 Dec;81(12):1253-8. doi: 10.1111/j.1349-7006.1990.tb02687.x.
3
Expression of two cytochromes P450 involved in carcinogen activation in a human colon cell line.
参与致癌物激活的两种细胞色素P450在人结肠癌细胞系中的表达。
Mol Cell Biochem. 1991 Mar 27;102(1):61-9. doi: 10.1007/BF00232158.
4
Species difference among experimental rodents in induction of P450IA family enzymes by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶诱导实验啮齿动物P450IA家族酶的种属差异。
Jpn J Cancer Res. 1992 Oct;83(10):1047-51. doi: 10.1111/j.1349-7006.1992.tb02720.x.