NAD(P)H NITROBLUE TETRAZOLIUM REDUCTASE LEVELS IN APPARENTLY NORMOXIC TISSUES - A HISTOCHEMICAL-STUDY CORRELATING ENZYME-ACTIVITY WITH BINDING OF RADIOLABELED MISONIDAZOLE

NAD(P)H NITROBLUE TETRAZOLIUM REDUCTASE LEVELS IN APPARENTLY NORMOXIC TISSUES - A HISTOCHEMICAL-STUDY CORRELATING ENZYME-ACTIVITY WITH BINDING OF RADIOLABELED MISONIDAZOLE
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DOI:
10.1038/bjc.1990.118
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发表时间:
1990-04-01
影响因子:
8.8
通讯作者:
NOLAN, J
NOLAN, J
中科院分区:
医学1区
文献类型:
--
作者:
COBB, LM;HACKER, T;NOLAN, J

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采用Hack和Helmy的NAD(P)H硝基蓝四唑还原酶活性组织化学鉴定方法,对小鼠某些细胞中的还原酶活性进行了定位。在以下部位观察到高活性:下呼吸道上皮、肝脏(小叶中心区)、眼睑(睑板腺和皮脂腺)、外阴腺和腮腺(小叶内导管的纹状细胞)。所有这些细胞先前已被鉴定为由米索硝唑(MISO)的酶还原形成的反应性代谢物的结合位点(Cobb等人,1989年)。以前认为MISO结合仅在低氧组织(肿瘤和可能的肝脏)中大量发生,因为在含氧量正常的组织中,氧应该逆转最初的单电子酶还原,从而防止逐渐还原为活性物质。我们认为,上述组织(可能是含氧量正常的组织)中还原酶水平极高,显著促进了结合反应性MISO代谢物的蓄积。
Hack and Helmy''s method for the histochemical identification of NAD(P)H nitroblue tetrazolium reductase activity was employed to pinpoint reductase activity in certain cells in the mouse. High activity was observed in the following: lower airway epithelium, liver (centrilobular zone), eyelid (meibomian and sebaceous glands), vulval gland and parotid gland (striated cells of intralobular ducts). All of these cells had previously been identified as sites of binding of the reactive metabolites formed from the enzymic reduction of misonidazole (MISO) (Cobb et al., 1989). It had previously been thought that MISO binding would only take place in significant amounts in hypoxic tissues (tumor and possibly liver) since in normoxic tissues oxygen should reverse the initial one electron enzymic reduction, thus preventing progressive reduction to reactive species. We suggest that the very high levels of reductase in the above listed, probably normoxic, tissues contribute significantly to the accumulation of bound reactive MISO metabolite(s).