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A Comparative Study on the Cytogenetic Activity of Three Benzodiazepines In Vitro

机译：比较研究的细胞发生的活动三苯二氮卓类体外

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摘要

Even though benzodiazepines (BDZs) possess a leading place among drugs used as anxiolytics, sedatives, muscle relaxants, and anticonvulsants, their cytogenetic effects have not been widely studied in humans. Alprazolam (AZ), bromazepam (BZ), diazepam, and lorazepam (LZ) are some of the most commonly prescribed BDZs. Previous positive findings on diazepam's cytogenetic effects in human lymphocytes suggested additional investigation. In the present research, we explored the cytogenetic potential of AZ, BZ, and LZ in human lymphocyte cultures, using an expanded sample set, administering the under-investigation medications at final concentrations equivalent to oral dosage. As a biomarker of genotoxicity we used sister chromatid exchanges, one of the most sensitive methods reflecting DNA damage and/or subsequent DNA repair, and as a marker of cytostaticity we estimated the proliferation rate index. After 72 h of incubation in the cultures, all three BDZs caused a concentration-dependent, statistically significant increase of sister chromatid exchange frequency (p < 0.001) followed by a statistically significant decrease of proliferation rate index (p < 0.001) of lymphocytes. Our conclusive results suggest that AZ, BZ, and LZ, at concentrations equivalent to oral doses, exhibit statistically significant genotoxicity in human lymphocyte cultures.
机译：尽管苯二氮卓类(BDZs)拥有主要在药物作为抗焦虑药,镇静剂、肌肉松弛剂和抗惊厥药物,细胞遗传学的影响尚未广泛研究人类。(BZ),安定,氯羟去甲安定(LZ)的最常用的BDZs。积极发现安定的细胞遗传学人类淋巴细胞显示额外的效果调查。探讨了细胞遗传学AZ的潜力,BZ,和LZ在人类淋巴细胞文化中,使用一个扩大样本集,管理在调查中药物在最后浓度相当于口服剂量。生物标志物的基因毒性我们使用的妹妹染色单体交换,一个最敏感的方法反映出DNA损伤和/或后续DNA修复,cytostaticity我们的标志估计增殖率指数。h孵化的文化中,所有三个BDZs引起了浓度,统计姐妹染色单体交换的显著增加频率(p < 0.001),后跟一个统计增殖率指数的显著下降淋巴细胞(p < 0.001)。结果表明,阿兹、商务和LZ,浓度相当于口服剂量,展览统计上显著的基因毒性在人淋巴细胞的文化。

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