[核糖核苷酸还原酶——亚硝基甲基脲作用的“靶标”]。

D E Filatov, M E Kudriavtsev, L M Baĭder, V L Sharygin, K V Griakalov, M K Pulatova, D B Korman
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引用次数: 0

摘要

甲基亚硝基脲(MNU)的抗肿瘤和毒性作用是通过其代谢途径确定的。在生物体中,MNU受到水解分解和反硝化作用的影响。体内研究表明,腹腔注射治疗剂量的MNU可抑制小鼠脾脏的核糖核苷酸还原酶,从而抑制DNA合成。该效应可能与MNU的抗肿瘤作用有关。据估计,该酶的M2亚基发生了破坏。讨论了核糖核苷酸还原酶活性丧失与蛋白质合成抑制的关系。此外,还讨论了MNU由于DNA前体池不平衡而引起的致癌性和致突变性。发现了注射MNU后动物血液和脾脏中铁(3+)-转铁蛋白、铜蓝蛋白、高铁血红蛋白含量的变化。单次注射MNU后变化可逆,多次注射后变化不可逆。
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[Ribonucleotide reductase--a "target" of the action of nitrosomethylurea].

The antitumor and toxic effects of methylnitrosourea (MNU) are determined through its metabolic pathways. In organism MNU is subject to hydrolytic decomposition and denitrosation. It has been shown in vivo studies that MNU abdominal injections of therapeutic doses caused the inhibition of ribonucleotide reductase in mouse spleen, and therefore the DNA synthesis depress. The effect may apparently contribute to antitumor property of MNU. It has been estimated that destruction of M2 subunit of the enzyme is occurred. The relation between the loss of ribonucleotide reductase activity and the inhibition of protein synthesis was discussed. Besides, the cancerogenic and mutagenic properties of MNU were discussed as a result of imbalance of DNA precursor pools. Changes in contents of Fe(3+)-transferrin, ceruloplasmin, methemoglobin in blood and spleen of animals after MNU injections have been found. The changes were reversible after single MNU injection and became irreversible after multiple injections.

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