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(-)-小豆蔻明对小鼠体细胞的遗传毒性作用。

Genotoxic effects of (-)-cubebin in somatic cells of mice.

机构信息

Universidade Estadual Paulista, UNESP, Faculdade de Filosofia e Ciências, Departamento de Fonoaudiologia, Marília, SP, Brazil.

出版信息

J Appl Toxicol. 2011 Mar;31(2):185-9. doi: 10.1002/jat.1616. Epub 2010 Dec 6.

Abstract

(-)-Cubebin belongs to the dibenzylbutyrolactone lignan group, which is widely distributed in the plant kingdom. Because this compound shows interesting biological activities, it is extremely important to evaluate its possible genotoxic activity to allow its safe use in humans. Thus, the present study was performed to investigate the genotoxicity potential activity of (-)-cubebin assessed by two assays: micronucleus in bone marrow cells and comet test in peripheral blood leukocytes of Swiss mice. In the (-)-cubebin dose range-finding assays, the maximum tolerated dose was greater than 2000 mg kg(-1) . The compound was administered by an oral route at single doses of 250, 500 and 2000 mg kg(-1) body weight. Cytotoxicity was assessed by scoring 200 consecutive total polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE/NCE ratio). Under our experimental conditions, micronucleus and comet assays, respectively, showed that (-)-cubebin caused dose-related clastogenic and genotoxic effects in the somatic cells investigated. PCE/NCE ratio showed no cytotoxicity for the three doses of the compound. The data suggest caution in the ingestion of (-)-cubebin by humans, especially at high doses.

摘要

(-)-麻黄油属于二苄基丁内酯木脂素类,广泛分布于植物界。由于该化合物具有有趣的生物活性,因此评估其可能的遗传毒性活性对于允许其在人类中安全使用极为重要。因此,本研究通过微核试验和彗星试验评估了(-)-麻黄油的遗传毒性活性,该试验在瑞士小鼠的骨髓细胞和外周血白细胞中进行。在(-)-麻黄油剂量探索试验中,最大耐受剂量大于 2000mg/kg。该化合物经口服途径给药,单次剂量分别为 250、500 和 2000mg/kg 体重。通过对 200 个连续的总多色性(PCE)和正常色性(NCE)红细胞(PCE/NCE 比值)进行评分来评估细胞毒性。在我们的实验条件下,微核和彗星试验分别表明,(-)-麻黄油在研究的体细胞中引起了剂量相关性的断裂和遗传毒性作用。PCE/NCE 比值表明该化合物的三个剂量均无细胞毒性。这些数据表明,人类在摄入(-)-麻黄油时应谨慎,特别是在高剂量下。

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