Is DNA the Real Target of Antitumor Platinum Compounds
Is DNA the Real Target of Antitumor Platinum Compounds
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DNA是抗肿瘤铂化合物的真正靶标吗
DOI：
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发表时间：
1984
期刊：
影响因子：
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通讯作者：
M. Wright
中科院分区：
文献类型：
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作者：
J. Macquet;J. Butour;N. Johnson;H. Razaka;B. Salles;C. Vieussens;M. Wright
铂化合物，特别是顺式-Pt（NH3）2Cl 2，代表了临床上用于癌症化疗的一类新的有效抗肿瘤药物（1）。这些化合物的作用机制尚未阐明。抗肿瘤活性和细胞毒性与一对顺式不稳定配体的存在相关（2，3）。在顺式铂系列中，惰性配体调节这些活性，而不稳定配体影响动物毒性。发现带电和中性化合物以及动力学惰性和非常活跃的化合物具有抗肿瘤作用（2）。在细胞水平上，这些亲电分子与DNA、RNA和蛋白质结合（4）。然而，用顺式Pt（NH3）2Cl 2观察到的诱导、致突变性、原噬菌体和rec A蛋白诱导、修复缺陷菌株中的敏感性增加以及DNA合成抑制表明DNA是靶点（4）。一般认为，DNA合成的抑制是抗肿瘤特性的DNA功能紊乱（综述见参考文献4）。
Platinum compounds, particularly cis-Pt(NH3)2Cl2, represent a new class of effective antitumor drugs used clinically in cancer chemotherapy (1). The mechanism of action of these compounds is not yet elucidated. Antitumor activity and cytotoxicity have been correlated with the presence of a pair of cis labile ligands (2, 3). In a cis-Pt series, inert ligands modulate these activities whereas labile ligands influence toxicity in animals. Charged and neutral compounds as well as kinetically inert and very reactive ones were found antitumoral (2). At the cellular level, these electrophilic molecules bind to DNA, RNA and proteins (4). However, filamentation, mutagenicity, prophage and rec A protein induction, increased sensitivity in repair-deficient strains and inhibition of DNA synthesis observed with cis-Pt (NH3)2Cl2 indicate that DNA is a target (4). It is generally thought that inhibition of DNA synthesis is the perturbed DNA function responsible of the antitumor properties (for a review, see ref. 4).
睾丸癌作为可治愈肿瘤的模型：理查德和辛达·罗森塔尔基金会奖讲座。
影响因子：
11.2
作者：
Einhorn,LH
通讯作者：
Einhorn,LH