Mixed function oxidase in the mammary gland and liver microsomes of lactating rats. Effects of 3-methylcholanthrene and beta-naphthoflavone.
Mixed function oxidase in the mammary gland and liver microsomes of lactating rats. Effects of 3-methylcholanthrene and beta-naphthoflavone.
复制标题
哺乳大鼠乳腺和肝微粒体中的混合功能氧化酶。
DOI：
10.1016/0006-2952(82)90217-9
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发表时间：
1982
影响因子：
5.8
通讯作者：
Malejka-Giganti,D
中科院分区：
文献类型：
--
作者：
Ritter,CL;Malejka-Giganti,D
对哺乳期大鼠乳腺和肝微粒体中混合功能氧化酶的组成及相关酶的活性进行了检测。细胞色素b5，NADH和NADPH依赖的细胞色素还原酶活性分别为15-，6-和10倍，在乳腺比在肝微粒体。乳腺微粒体中细胞色素P-450（P-448）的测定需要消除血红蛋白和细胞色素的光谱干扰3。细胞色素氧化酶的活性也表明，后者在这一馏分中的存在。细胞色素aa 3减少乳腺微粒体厌氧孵育，在存在抗霉素A，与琥珀酸钠，吩嗪乙硫酸盐，和抗坏血酸钠在室温下30分钟。连二亚硫酸盐还原的细胞色素P-450（P-448）一氧化碳复合物的光谱分辨率发生在充气后30分钟。肝脏中细胞色素P-450的基础水平比乳腺微粒体中高约500倍。用肝细胞色素P-448诱导剂3-甲基胆蒽和β-萘酮预处理哺乳期大鼠，乳腺和肝微粒体中的细胞色素含量分别增加3- 10倍和2倍。用N-2-芴基乙酰胺测得的Ⅰ型结合光谱也显示了两种组织微粒体中细胞色素P-448的诱导作用。用苯并[a]芘和N-2-芴基乙酰胺的羟基化作为混合功能氧化酶活性的量度，我们发现，在用诱导剂处理大鼠后，肝微粒体中的基础活性增加了4- 8倍。0.1mM α-萘酚酮可抑制该酶的诱导活性，表明该酶依赖于细胞色素P-448。这些数据表明，乳腺，一个肝外的目标，致癌物，是能够代谢。
Mammary gland and liver microsomes of lactating rats were examined for the components of mixed function oxidase and related enzyme activities. Cytochromeb5, NADH- and NADPH-dependent cytochromecreductase activities were 15-, 6- and 10-fold lower, respectively, in the mammary gland than in the liver microsomes. The determination of cytochrome P-450 (P-448) in the mammary gland microsomes required elimination of the spectral interferences by hemoglobin and cytochromeaa3. The presence of the latter in this fraction was also shown by cytochromecoxidase activity. Cytochromeaa3was reduced by anaerobic incubation of mammary gland microsomes, in the presence of antimycin A, with sodium succinate, phenazine ethosulfate, and sodium ascorbate for 30 min at room temperature. Spectral resolution of the dithionite-reduced cytochrome P-450 (P-448) carbon monoxide complex occurred 30 min after gassing. The basal level of cytochrome P-450 was about 500-fold greater in the liver than in the mammary gland microsomes. Pretreatment of lactating rats with the inducers of hepatic cytochrome P-448, 3-methylcholanthrene and β-naphthoflavone, increased the cytochrome content 3- to 10-fold and 2-fold, in the mammary gland and liver microsomes, respectively. The induction of cytochrome P-448 in microsomes of both tissues was also shown by type I binding spectra obtained withN-2-fluorenylacetamide. Using hydroxylation of benzo[a]pyrene andN-2-fluorenylacetamide as a measure of mixed function oxidase activity, we found that the basal activities, which were 4- to 8-fold greater in the liver microsomes, were increased in both tissues after treatment of rats with the inducers. The induced activities were inhibited by 0.1 mM α-napthoflavonein vitro, indicating a dependence on cytochrome P-448. The data suggest that the mammary gland, an extrahepatic target for carcinogens, is capable of their metabolism.