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首页> 外文期刊>Egyptian Journal of Medical Human Genetics >Evaluation of chromosomal aberrations induced by hydralazine in Chinese hamster ovary cells
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Evaluation of chromosomal aberrations induced by hydralazine in Chinese hamster ovary cells

机译：肼苯哒嗪诱导的中国仓鼠卵巢细胞染色体畸变的评估

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Background and purpose Hydralazine (HDZ) is a cardiovascular drug that is widely used to treat hypertension. The present study was done to assess the cytogenetic effects of HDZ on Chinese hamster ovary (CHO) cells. Materials and methods Methylthiazol tetrazolium (MTT) assay was carried out to determine the half maximal inhibitory concentration (IC 50 ) of the drug. The IC 50 value for HDZ was 243.3±16.9μg/ml. To investigate the clastogenic effects of the drug, chromatid breaks and polyploidy in metaphases were analyzed. CHO cells were exposed to different concentrations of HDZ (20 and 40μg/ml) for 24h. The experiments were carried out in the presence and absence of metabolic activation system (S9 mix; 1ml S9 mix contained: 0.3ml phosphate solutions, 0.2ml KCl, 0.2ml MgCl 2 , 0.1ml S9 fraction, 0.1ml G-6-P and 0.1ml NADP), because HDZ is metabolized in the liver. Mitomycin-C and sodium arsenite were used as positive controls. Results In the absence of S9 fraction, the level of chromatid breaks statistically increased ( P =0.011) and mitotic index significantly decreased ( P <0.001) in CHO cells treated with HDZ. There was no significant difference between treated and untreated CHO cells with HDZ for the level of polyploidy ( F =0.05; df=2, 6; P =0.945). In the presence of S9 fraction, although the mitotic index elevated, still there was a significant difference between control and treated cells ( F =50.53; df=2, 6; P <0.001). There was no significant difference between 20μg/ml of HDZ (+S9) and untreated cells for frequency of chromatid breaks. However, at the 40μg/ml concentration of HDZ (+S9), there was a significant difference between treated and untreated cells. Conclusion HDZ have genotoxic effects on CHO cells in their non-toxic dose, but S9 mix addition decreased these effects.
机译：背景与目的肼屈嗪（HDZ）是一种心血管药物，被广泛用于治疗高血压。本研究旨在评估HDZ对中国仓鼠卵巢（CHO）细胞的细胞遗传学作用。材料和方法进行了甲基噻唑四唑（MTT）分析，以确定该药物的半数最大抑制浓度（IC 50）。 HDZ的IC 50值为243.3±16.9μg/ ml。为了研究药物的杀乳作用，分析了中期的染色单体断裂和多倍性。将CHO细胞暴露于不同浓度的HDZ（20和40μg/ ml）中24h。实验在存在和不存在代谢激活系统的情况下进行（S9混合物; 1ml S9混合物包含：0.3ml磷酸盐溶液，0.2ml KCl，0.2ml MgCl 2，0.1ml S9馏分，0.1ml G-6-P和0.1ml NADP），因为HDZ在肝脏中代谢。丝裂霉素C和亚砷酸钠用作阳性对照。结果在不存在S9组分的情况下，HDZ处理的CHO细胞的染色单体断裂水平显着增加（P = 0.011），有丝分裂指数显着降低（P <0.001）。 HDZ处理的和未处理的CHO细胞之间的多倍性水平没有显着差异（F = 0.05; df = 2，6; P = 0.945）。在存在S9级分的情况下，尽管有丝分裂指数升高，但在对照细胞和处理过的细胞之间仍然存在显着差异（F = 50.53; df = 2，6; P <0.001）。 HDZ（+ S9）和未处理细胞的20μg/ ml之间的染色单体断裂频率没有显着差异。但是，在HDZ（+ S9）浓度为40μg/ ml时，处理过的和未处理过的细胞之间存在显着差异。结论HDZ以其无毒剂量对CHO细胞具有遗传毒性作用，但S9混合剂的添加降低了这些作用。

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