革兰氏阴性菌粘质沙雷氏菌的核酸酶在治疗剂量下具有弱细胞毒性

M. Filimonova
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摘要

粘多糖核酸酶在同源非特异性核酸酶家族中居首位。对其栽培特点、结构、作用机理及一些物理、化学和生化特性进行了较深入的研究。它有两种同工异构体,不同的是n端片段和一些性质。这种核酸酶在小鼠身上显示出抑制癌症的作用。它是抗狂犬病组合物的关键成分,可提高感染小鼠的存活率。它的功效与肺部疾病治疗期间用于气道清洁的Pulmozyme®相似。本研究的目的是分析不同浓度的粘质葡萄球菌核酸酶及其分离异构体的细胞毒性作用。为了确定细胞毒性,我们使用MTT试验和人类细胞培养结肠直肠癌-HCT 116,乳腺癌MCF-7和正常皮肤成纤维细胞。结果表明,在接近治疗剂量的细胞培养基中,每1 ml细胞培养基中含有0.2 - 25µg的核酸酶,显示出微弱的细胞毒性作用。这种效应与酶活性的丧失无关。这两种同工异构体的IC50相似。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Nuclease from Gram-Negative Bacteria Serratia Marcescens is Weakly Cytotoxic at Therapeutic Doses
The nuclease from S.marcescens heads a family of homological nonspecific nucleases. Its cultivation features, structure, mechanism of action, some physical, chemical and biochemical properties are well studied. It is presented by two isoforms, differing by N-terminal fragment and some properties. The nuclease demonstrated a cancer suppressing effect in mice. It is a key component of the anti-rabies composition which increases survival of the infected mice. It is similar by its efficiency to Pulmozyme® that is used for airway cleansing during the treatment of pulmonary diseases. The aim of the study was to analyze a cytotoxic effect of S. marcescens nuclease and its separate isoforms at different concentrations. To determine the cytotoxicity we used MTT assay and human cell cultures of colorectal cancer -HCT 116, breast cancer MCF-7 and normal skin fibroblasts. Results show that the nuclease demonstrates a weak cytotoxic effect at the amounts of 0.2 – 25 µg per 1 ml of the cell culture medium that is close to its therapeutic doses. This effect is not connected with the loss of the enzymatic activity. The isoforms are similar by their IC50.
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