O6-methylguanine-DNA methyltransferase activity in human liver tumors.
O6-methylguanine-DNA methyltransferase activity in human liver tumors.
复制标题
人肝脏肿瘤中的 O6-甲基鸟嘌呤-DNA 甲基转移酶活性。
DOI：
10.1093/carcin/12.7.1313
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发表时间：
1991
期刊：
影响因子：
4.7
通讯作者：
Mituo Ikenaga
中科院分区：
文献类型：
--
作者：
G. Isowa;Kanji Ishizaki;Tetsuo Sadamoto;Koichi Tanaka;Yoshio Yamaoka;Kazue Ozawa;Mituo Ikenaga
先前的研究表明，在大约五分之一的人类肿瘤细胞株中，能够修复烷基化剂产生的DNA中的o6 -烷基鸟嘌呤的o6 -甲基鸟嘌呤-DNA甲基转移酶（MGMT）活性缺乏。这些菌株被称为Mer细胞。为了观察是否存在缺乏MGMT活性的人类肿瘤，我们测量了21例患者肝脏肿瘤提取物中的MGMT活性，并将其与来自同一患者的正常瘤周组织的活性进行了比较。通过测量从含有[甲基3H]标记的o6 -甲基鸟嘌呤的底物DNA转移到酸不溶性蛋白质片段的3H放射性来检测MGMT活性。不同提取物间MGMT活性差异较大；个体间差异在正常肝组织中约为6倍，在肝肿瘤中则大得多。尽管在许多情况下，在肝脏肿瘤和正常组织中都发现了相似的高水平MGMT活性，但与同一患者的正常肝组织相比，有6个肿瘤的活性比正常肝组织低3倍以上。尽管相应的正常肝脏样本显示出显著的活性，但根据目前的方法，来自两名患者的肝脏肿瘤没有任何可检测到的MGMT活性水平。我们还测量了同一组织提取物中两种常见酶的活性，谷丙转氨酶（GPT）和乳酸脱氢酶（LDH）。MGMT活性未检测到的肝肿瘤样本中GPT和LDH的活性与周围正常肝组织相似。这些结果可能提示存在人类肿瘤，缺乏或非常低的MGMT活性。
Previous studies have shown that in about one-fifth of human tumor cell strains, the activity of O6-methylguanine-DNA methyltransferase (MGMT), which can repair O6-alkylguanine in DNA produced by alkylating agents, is deficient. These strains are termed Mer- cells. To see if there is any human tumor lacking MGMT activity, we measured the MGMT activity in extracts from liver tumors of 21 patients, and compared it to the activity in normal peritumoral tissues derived from the same patients. The MGMT activity was assayed by measuring the 3H radioactivity transferred from the substrate DNA containing [methyl-3H]-labeled O6-methylguanine to an acid-insoluble protein fraction. There was considerable variation in MGMT activity among individual extracts; the interindividual variation was approximately 6-fold in normal liver tissue and much larger in liver tumors. Although in many cases similar high levels of MGMT activity were found both in liver tumors and in the normal counterpart, six tumors had greater than 3-fold less activity compared with the normal liver tissue from the same patient. Liver tumors from two patients did not have any detectable level of MGMT activity by the present method used, in spite of the fact that the corresponding normal liver samples demonstrated significant activities. We also measured in the same tissue extracts the activities of two common enzymes, glutamic pyruvic transaminase (GPT) and lactic dehydrogenase (LDH). The activities of GPT and LDH in the liver tumor samples that showed undetectable levels of MGMT activity were similar to those in the surrounding normal liver tissues. These results may suggest the existence of human Mer- tumors, deficient or very low MGMT activity.