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γ-谷氨酰转肽酶在二甲基苯并[a]蒽诱导的乳腺腺癌及荷瘤大鼠肝脏中的情况

gamma-Glutamyltranspeptidase in dimethylbenz[a]anthracene-induced mammary adenocarcinomas and in livers of tumor bearing rats.

作者信息

Sulakhe S J

出版信息

Int J Biochem. 1987;19(6):509-15. doi: 10.1016/0020-711x(87)90134-0.

DOI:10.1016/0020-711x(87)90134-0
PMID:2886376
Abstract

A single dose of dimethylbenz[a]anthracene (DMBA) at 20 mg/kg resulted in 100% incidence of intraductal mammary adenocarcinomas in Wistar rats, the large tumors averaging 1.87 +/- 0.45 g. gamma-Glutamyltranspeptidase activities were elevated in DMBA-induced mammary adenocarcinomas relative to lactating mammary tissue in all fractions examined: 18.8-fold in homogenates; 22.1-fold in particulate fractions; and 5.7-fold in supernatant fractions. In DMBA-induced mammary adenocarcinomas, gamma-glutamyltranspeptidase was 95% particulate, 5% supernatant, whereas in lactating mammary tissue, gamma-glutamyltranspeptidase was equally distributed between particulate and supernatant fractions. Particulate gamma-glutamyltranspeptidase from DMBA-induced mammary adenocarcinomas as well as lactating mammary tissue displayed classical Michaelis-Menten characteristics: for the adenocarcinoma enzyme Km was 2.5 nM and Vmax 200 nmol mg-1 min-1; for mammary tissue enzyme Km was 2.5 nM and Vmax 11.1 nmol X mg-1 X min-1. Both particulate enzymes were activated at 50 degrees C relative to 37 degrees C to the same extent: 1.37-fold. The activities of gamma-glutamyltranspeptidase were increased 1.8-fold in the livers of rats bearing DMBA-induced mammary adenocarcinomas relative to age-matched controls. Plasma levels of gamma-glutamyltranspeptidase were also increased 1.6-fold in tumor bearing rats. There was no observable sign of liver damage in tumor bearing rats; plasma glutamic pyruvic transaminase levels were normal in these animals. Blood glucose levels were elevated 17% in rats bearing DMBA-induced mammary adenocarcinomas compared to age-matched controls, although plasma insulin levels were the same in both groups: 35.4 +/- 3.5 microIU/ml for the former; 31.9 +/- 3.1 microIU/ml for the latter.

摘要

以20毫克/千克的剂量给Wistar大鼠单次注射二甲基苯并[a]蒽(DMBA),会导致乳腺导管内腺癌的发生率达到100%,大肿瘤平均重量为1.87±0.45克。在所有检测的组分中,相对于泌乳乳腺组织,DMBA诱导的乳腺腺癌中γ-谷氨酰转肽酶活性均升高:匀浆中升高18.8倍;微粒体组分中升高22.1倍;上清液组分中升高5.7倍。在DMBA诱导的乳腺腺癌中,γ-谷氨酰转肽酶95%存在于微粒体中,5%存在于上清液中,而在泌乳乳腺组织中,γ-谷氨酰转肽酶在微粒体和上清液组分中分布均匀。DMBA诱导的乳腺腺癌以及泌乳乳腺组织中的微粒体γ-谷氨酰转肽酶均表现出典型的米氏动力学特征:腺癌酶的Km为2.5纳摩尔,Vmax为200纳摩尔·毫克-1·分钟-1;乳腺组织酶的Km为2.5纳摩尔,Vmax为11.1纳摩尔·毫克-1·分钟-1。两种微粒体酶在50℃时相对于37℃的激活程度相同:均为1.37倍。相对于年龄匹配的对照组,患有DMBA诱导的乳腺腺癌的大鼠肝脏中γ-谷氨酰转肽酶活性增加了1.8倍。荷瘤大鼠血浆中γ-谷氨酰转肽酶水平也增加了1.6倍。荷瘤大鼠没有可观察到的肝损伤迹象;这些动物的血浆谷丙转氨酶水平正常。与年龄匹配的对照组相比,患有DMBA诱导的乳腺腺癌的大鼠血糖水平升高了17%,尽管两组的血浆胰岛素水平相同:前者为35.4±3.5微国际单位/毫升;后者为31.9±3.1微国际单位/毫升。

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