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人腮腺沃辛瘤和黏液表皮样癌中谷胱甘肽S-转移酶、DT-二氢嘧啶脱氢酶以及一种明显具有肿瘤特异性的胞质3类醛脱氢酶的过表达。

Over-expression of glutathione S-transferases, DT-diaphorase and an apparently tumour-specific cytosolic class-3 aldehyde dehydrogenase by Warthin tumours and mucoepidermoid carcinomas of the human parotid gland.

作者信息

Sreerama L, Sladek N E

机构信息

Department of Pharmacology, University of Minnesota Medical School, Minneapolis 55455, USA.

出版信息

Arch Oral Biol. 1996 Jun;41(6):597-605. doi: 10.1016/0003-9969(96)00005-2.

DOI:10.1016/0003-9969(96)00005-2
PMID:8937651
Abstract

Cytosolic class-3 aldehyde dehydrogenase (ALDH-3) may help to protect organisms from certain environmental aldehydes by catalysing their detoxification. Consistent with this notion are the reports that relatively high levels of this enzyme are present in tissues, e.g. stomach mucosa and lung, that are so-called ports of entry for such agents. Further, it is found in human saliva. The present investigation revealed that small amounts of this enzyme are also present in human salivary glands; mean values for ALDH-3 activities (NADP-dependent enzyme-catalysed oxidation of benzaldehyde) in cytosolic fractions prepared from submandibular and parotid glands were 52 (range: 29-92) and 44 (range: 13-73) mIU/g tissue, respectively. Essentially identical or slightly lower levels of this enzyme activity were found in pleomorphic adenomas, an undifferentiated carcinoma, and an adenocystic carcinomas, of the parotid gland. On the other hand, Warthin tumours, and mucoepidermoid carcinomas of the parotid gland exhibited relatively elevated levels of ALDH-3 activity; mean values were 1200 (range: 780-1880) and 810 (range: 580-1200) mIU/g tissue, respectively. The ALDH-3 found in normal salivary glands was, as judged by physical, immunological and kinetic criteria, identical to human stomach mucosa ALDH-3 whereas the ALDH-3 present in Warthin tumours, and mucoepidermoid carcinomas, of the parotid gland appeared to be a subtle variant thereof. Qualitatively paralleling the relatively elevated ALDH-3 levels in mucoepidermoid carcinomas and Warthin tumours were relatively elevated levels of glutathione S-transferase (alpha and pi) and DT-diaphorase. As was the case with ALDH-3 levels, glutathione S-transferase (alpha and pi) and DT-diaphorase levels were not elevated in pleomorphic adenomas. Glutathione S-transferase mu was not detected in the two normal parotid gland samples, or in the single pleomorphic adenoma sample, tested. It was found in the single mucoepidermoid carcinoma sample, and in one of the two Warthin tumour samples tested. Cellular levels of ALDH-3, glutathione S-transferases and/or DT-diaphorase could be useful criteria when the decision to be made is whether a salivary gland tumour is a mucoepidermoid carcinoma. ALDH-3 and glutathione S-transferases are known to catalyse the detoxification of two agents that are used to treat salivary gland tumours, viz. cyclophosphamide and cisplatin, respectively. Thus, elevated levels of these enzymes in the mucoepidermoid carcinomas must account for, or at least contribute to, the relative ineffectiveness of these agents when used to treat this tumour.

摘要

胞质3类醛脱氢酶(ALDH-3)可通过催化某些环境醛的解毒作用,帮助保护生物体免受其害。与此观点一致的是,有报道称该酶在组织中含量相对较高,例如胃黏膜和肺等这些所谓的此类物质进入机体的入口部位。此外,在人的唾液中也能发现它。目前的研究表明,人唾液腺中也存在少量这种酶;从下颌下腺和腮腺制备的胞质组分中,ALDH-3活性(NADP依赖性酶催化的苯甲醛氧化)的平均值分别为52(范围:29 - 92)和44(范围:13 - 73)mIU/g组织。在腮腺的多形性腺瘤、未分化癌和腺囊性癌中发现该酶活性基本相同或略低。另一方面,腮腺的沃辛瘤和黏液表皮样癌中ALDH-3活性相对较高;平均值分别为1200(范围:780 - 1880)和810(范围:580 - 1200)mIU/g组织。从物理、免疫学和动力学标准判断,正常唾液腺中发现的ALDH-3与人类胃黏膜ALDH-3相同,而腮腺沃辛瘤和黏液表皮样癌中存在的ALDH-3似乎是其一种细微变体。黏液表皮样癌和沃辛瘤中ALDH-3水平相对升高,与之定性平行的是谷胱甘肽S-转移酶(α和π)和DT-黄递酶水平也相对升高。与ALDH-3水平情况相同,多形性腺瘤中谷胱甘肽S-转移酶(α和π)和DT-黄递酶水平未升高。在所检测的两个正常腮腺样本或单个多形性腺瘤样本中未检测到谷胱甘肽S-转移酶μ。在单个黏液表皮样癌样本以及所检测的两个沃辛瘤样本中的一个中发现了它。当需要判断唾液腺肿瘤是否为黏液表皮样癌时,细胞内ALDH-3、谷胱甘肽S-转移酶和/或DT-黄递酶水平可能是有用的标准。已知ALDH-3和谷胱甘肽S-转移酶分别催化用于治疗唾液腺肿瘤的两种药物即环磷酰胺和顺铂的解毒作用。因此,黏液表皮样癌中这些酶水平升高必定是这些药物用于治疗该肿瘤时相对无效的原因,或者至少对此有影响。

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