Genotoxic effects of extremely low frequency (ELF) magnetic fields (MF) evaluated by the Tradescantia-micronucleus assay

Extremely low frequency (ELF) electric fields (EF) and magnetic fields (MF) are generated during the production, transmission, and use of electrical energy. Although epidemiology studies suggest that there is a cancer risk associated with exposure to ELF-MF, short-term genotoxicity assays with bacteria and mammalian cells have produced inconsistent results. In the present study, we investigated the possible genotoxicity of ELF-MF by using the Tradescantia-micronucleus (Trad-MN) assay, a sensitive, reproducible, well-standardized assay for genotoxicity testing. A 50 Hz ELF-MF was generated by a laboratory exposure system consisting of a pair of parallel coils in a Helmholtz configuration. Exposure of Tradescantia (clone # 4430) inflorescences to the ELF-MF, at a flux density (B) corresponding to 1 mT, for 1, 6, and 24 h resulted in a time-dependent increase in MN frequency. The results indicate that a 50 Hz MF of 1 mT field strength is genotoxic in the Trad-MN bioassay and suggest that this assay may be suitable as a biomonitor for detecting the genotoxicity of ELF-MF in the field.     

An alkaline comet assay study on the antimalarial drug atovaquone in human peripheral blood lymphocytes: a study based on clinically relevant concentrations

Atovaquone, a hydroxynaphthoquinone, is an anti‐parasite drug, selectively targeting the mitochondrial respiratory chain of malaria parasite. It is used for both the treatment and prevention of malaria, usually in a fixed combination with proguanil. Although atovaquone has not often been associated with severe adverse reactions in the recommended dosages and has a relatively favorable side effect profile, the present study was undertaken to evaluate its cytogenotoxic potential towards human peripheral blood lymphocytes. Two different concentrations of atovaquone found in plasma when used in fixed‐dose combination with proguanile hydrochloride were used with and without S9 metabolic activation: 2950 ng ml^?1 used for prophylactic treatment and 11 800 ng ml^?1 used in treatment of malaria. The results showed that lymphocyte viability was not affected after the treatment, suggesting that atovaquone was not cytotoxic in the given concentrations. With the alkaline comet assay we demonstrated that in human peripheral blood lymphocytes no significant changes in comet parameters occurred after the treatment. There were no differences in tested parameters with the addition of S9 metabolic activation, indicating that atovaquone either has no metabolite or it is not toxic in the given concentrations. Since no effects were observed after the treatment, it is to be concluded that atovaquone is safe from the aspect of genototoxicity in the recommended dosages. Copyright © 2011 John Wiley & Sons, Ltd.     

桦木酸抗炎作用与机制

目的 对桦木酸的抗炎作用与机制进行综述。方法 检索归纳有关桦木酸抗炎作用的文献,对其作用途径及机制进行了分析。结果 桦木酸对实验性炎症模型及其他模型有显著的抗炎作用,桦木酸抗炎作用机制涉及糖皮质激素受体、一氧化氮、氧化应激、免疫调节、细胞因子和黏附分子、炎性信号通路等。此外,桦木酸与其他天然产物还有协同的抗炎作用。结论 桦木酸通过多途径发挥抗炎作用,抗炎活性研究对于探讨桦木酸治疗疾病的作用机制有着重要意义。     

小檗碱对多柔比星的增效减毒作用及其机制研究进展

多柔比星是临床治疗中有效的抗肿瘤药,但其严重的心脏、肝脏毒性使其临床应用受到了极大限制。小檗碱是从黄连属植物分得的生物碱,具有多种生物活性和药理作用,对痢疾、真菌感染、糖尿病、肿瘤等都有治疗作用。研究发现小檗碱不仅可以通过诱导肿瘤细胞的凋亡来增强多柔比星的抗肿瘤活性;还可以通过改变多柔比星引起心肌病的相关指标来降低多柔比星引起的心肌细胞的损伤;另外,小檗碱对多柔比星引起的肝脏损伤也有一定的保护作用。综述了小檗碱对多柔比星的增效减毒作用及其机制的研究进展,这种发现提供了一种新颖的治疗方法,对多柔比星临床治疗的发展具有重要的意义。     

黄芪、血竭对血栓和烧烫伤的协同作用研究

目的观察黄芪和血竭对大鼠血栓形成和烧烫伤愈合方面的协同作用。方法通过黄芪、血竭对大鼠体外血栓形成及大鼠深Ⅱ度蒸气烧烫伤的实验研究,评价其功效,同时观察二者之间有无协同作用。结果黄芪、血竭、复方黄芪血竭制剂均有明显抗血栓的作用（P〈0．05）,复方黄芪血竭制剂在抗血栓实验中缩短血栓长度和减轻血栓湿质量、干质量作用更明显（P〈0．05）;黄芪、血竭和复方黄芪血竭制剂均可促进大鼠烧烫伤的愈合（P〈0．05）,复方黄芪血竭制剂在早期6～11d对烧烫伤愈合的促进作用更明显（P〈0．05）。结论黄芪和血竭复方制剂在抗血栓和促进烧烫伤早期愈合方面有显著协同作用。     

Cytotoxic and Genotoxic Effects of Cyanobacterial and Algal Extracts—Microcystin and Retinoic Acid Content

In the last decade, it has become evident that complex mixtures of cyanobacterial bioactive substances, simultaneously present in blooms, often exert adverse effects that are different from those of pure cyanotoxins, and awareness has been raised on the importance of studying complex mixtures and chemical interactions. We aimed to investigate cytotoxic and genotoxic effects of complex extracts from laboratory cultures of cyanobacterial species from different orders (Cylindrospermopsis raciborskii, Aphanizomenon gracile, Microcystis aeruginosa, M. viridis, M. ichtyoblabe, Planktothrix agardhii, Limnothrix redekei) and algae (Desmodesmus quadricauda), and examine possible relationships between the observed effects and toxin and retinoic acid (RA) content in the extracts. The cytotoxic and genotoxic effects of the extracts were studied in the human hepatocellular carcinoma HepG2 cell line, using the MTT assay, and the comet and cytokinesis-block micronucleus (cytome) assays, respectively. Liquid chromatography electrospray ionization mass spectrometry (LC/ESI-MS) was used to detect toxins (microcystins (MC-LR, MC-RR, MC-YR) and cylindrospermopsin) and RAs (ATRA and 9cis-RA) in the extracts. Six out of eight extracts were cytotoxic (0.04–2 mg_DM/mL), and five induced DNA strand breaks at non-cytotoxic concentrations (0.2–2 mg_DM/mL). The extracts with genotoxic activity also had the highest content of RAs and there was a linear association between RA content and genotoxicity, indicating their possible involvement; however further research is needed to identify and confirm the compounds involved and to elucidate possible genotoxic effects of RAs.     

哺乳动物细胞染色体畸变试验的标准化与背景数据采集

染色体畸变试验作为保健食品、化妆品、药品、医疗器械上市前常规开展的毒理学试验项目,是检测化学物质对染色体数量和结构影响的基本方法。确立标准化试验方法并积累一定的背景数据,是试验系统和数据真实可靠性的有力保障,可为科研人员和审评专家的数据分析提供有力依据。首先就影响染色体畸变试验结果的因素进行简要综述,继而通过回顾国内外2012-2017年期间发表的47篇有关哺乳动物细胞染色体畸变试验的研究来讨论如何规范化试验条件,并以国家药物安全评价监测中心2002-2017年汇总的背景数据为例阐释建立历史背景数据的要点。总之,严格参考OECD指导原则开展规范化的染色体畸变试验并通过长期积累建立一套对照受试物的背景数据是临床前遗传毒性研究的关键环节,有利于更好地对药物等受试物的潜在致染色体损伤作用进行合理而有效的判断。     

Ames波动试验和GADD45a-GFP GreenScreen两种快速筛选方法评价大黄素和芫花素的遗传毒性

目的 使用Ames波动试验和GADD45a-GFP GreenScreen两种快速筛选方法,对有毒中药芫花和了哥王的主要单体成分大黄素和芫花素的遗传毒性进行评价。方法 （1）Ames波动试验：在非代谢活化（-S9）和代谢活化（+S9）条件下使用鼠伤寒沙门菌TA100开展基于96孔液态培养法的细菌回复性突变试验,大黄素和芫花素（终质量浓度范围均为0.1~10 μg/mL）与菌液充分混合后在37℃下培养72 h。（2）GADD45a GreenScreen高通量筛选试验：在非代谢活化（-S9）和代谢活化条件下（+S9）将表达GADD45a基因的TK细胞（GenM-T01和GenM-C01）与大黄素（0.13~32.0 μg/mL）和芫花素（0.07~16.0 μg/mL）分别作用48 h（-S9）和3 h（+S9）,之后通过酶标仪和流式细胞仪检测绿色荧光蛋白（enhanced green fluorescent protein,EGFP）的荧光强度。结果 有无代谢活化条件下,10 μg/mL大黄素均可诱导TA100的回复性突变率显著性升高（P<0.05、P<0.001）;代谢活化条件下,10 μg/mL芫花素可诱导TA100的回复性突变率显著性升高（P<0.001）,16.0 μg/mL芫花素诱导TK6细胞表达的GADD45a-EGFP荧光强度也超过了遗传毒性阈值（1.3倍）。结论 当前研究提示大黄素和芫花素为可疑遗传毒性,需要开展深入研究明确其遗传毒性及机制。Ames波动试验和GADD45a GreenScreen是良好的高通量筛选备选试验,可极大优化浩繁的药物的毒性筛选工作,尤其适宜诸如中药等成分和配伍复杂的药物。