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在4-硝基喹啉-N-氧化物还原酶活性的口腔内位点与化学致癌作用之间发现了一种关系。

A relationship found between intra-oral sites of 4NQO reductase activity and chemical carcinogenesis.

作者信息

Booth D R

机构信息

Department of Pathology, Queen Elizabeth II Medical Centre, Hollywood, Western Australia.

出版信息

Cell Tissue Kinet. 1990 Jul;23(4):331-40. doi: 10.1111/j.1365-2184.1990.tb01129.x.

DOI:10.1111/j.1365-2184.1990.tb01129.x
PMID:2117996
Abstract

Topical application on rat oral mucosa of the chemical 4-nitroquinoline 1-oxide (4NQO) has been shown to produce squamous cell carcinomas on the posterior tongue and/or the posterior hard palate. 4NQO is broken down in vivo by a diaphorase, 4NQO reductase (E.C.1.6.99.2), to produce an active molecule believed to be responsible for carcinogenesis. It has been shown that there are higher concentrations of 4NQO reductase in oesophageal mucosa compared with elsewhere in the gastrointestinal tract. The purpose of these experiments was to compare the distribution of certain diaphorases in the oral mucosa. Samples of rat tongue and cheek epithelia were homogenized, then ultracentrifuged to provide mixed cytosol and microsome fractions from the epithelial cells. A spectrophotometer was used to measure the variation in absorbance at 340 nm of NADH consumed by reduction of 4NQO by enzymes present in the tissue extracts. A histochemical technique was used to compare the activity of NADH diaphorase, NADP diaphorase and glucose-6-phosphate dehydrogenase at different sites of the oral mucosa. Statistical analysis showed that there were significant (P less than 0.01) differences between the activities of all three enzymes at different sites of the oral mucosa. In each case, a higher activity was found at the sites of high incidence of squamous cell carcinoma. A lower activity was found at sites where carcinomas did not occur.

摘要

已证实,将化学物质4-硝基喹啉-1-氧化物(4NQO)局部应用于大鼠口腔黏膜会在舌后部和/或硬腭后部诱发鳞状细胞癌。4NQO在体内会被一种黄递酶——4NQO还原酶(E.C.1.6.99.2)分解,产生一种被认为是致癌原因的活性分子。研究表明,与胃肠道其他部位相比,食管黏膜中4NQO还原酶的浓度更高。这些实验的目的是比较某些黄递酶在口腔黏膜中的分布情况。将大鼠舌和颊上皮的样本匀浆,然后进行超速离心,以提供来自上皮细胞的混合胞质溶胶和微粒体部分。使用分光光度计测量组织提取物中存在的酶将4NQO还原所消耗的NADH在340nm处吸光度的变化。采用组织化学技术比较口腔黏膜不同部位的NADH黄递酶、NADP黄递酶和葡萄糖-6-磷酸脱氢酶的活性。统计分析表明,口腔黏膜不同部位这三种酶的活性之间存在显著差异(P小于0.01)。在每种情况下,鳞状细胞癌高发部位的酶活性较高。在未发生癌的部位,酶活性较低。

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