豆类丝核菌次级代谢产物的遗传毒性与致突变作用

通过小鼠骨髓染色体畸变试验、睾丸染色体畸变试验及鼠伤寒沙门氏菌回复试验考察豆类丝核菌次级代谢产物的遗传毒性与致突变性。结果显示,豆类丝核菌次级代谢产物对小鼠骨髓染色体及睾丸染色体均无致畸变作用;Ames试验结果显示在本次试验的各个浓度下无论是加入活化系统(S-9混合液)还是不加,回变菌落数均未大于自然回变菌落的2倍,而各阳性对照组均显示强烈的诱变作用,表明,本次试验剂量和条件下,豆类丝核菌次级代谢产物未见遗传毒性和致突变作用。     

(Q)SAR tools for the prediction of mutagenic properties: Are they ready for application in pesticide regulation?

The assessment of human health risks resulting from the presence of metabolites in groundwater and food residues has become an important element in pesticide authorisation. In this context, the evaluation of mutagenicity is of particular interest and a paradigm shift from exposure‐triggered testing to in silico‐based screening has been recommended in the European Food Safety Authority (EFSA) Guidance on the establishment of the residue definition for dietary risk assessment. In addition, it is proposed to apply in silico predictions when experimental mutagenicity testing is not possible due to a lack of sufficient quantities of the pesticide metabolite. This, combined with animal welfare and economic considerations, has led to a situation where an increasing number of in silico studies are submitted to regulatory authorities. Whilst there is extensive experience with in silico predictions for mutagenicity in the chemical and pharmaceutical industry, their suitability in pesticide regulation is still insufficiently considered. Therefore, we herein discuss critical issues that need to be resolved to successfully implement (Quantitative) Structure‐Activity Relationship ((Q)SAR) as an accepted tool in pesticide regulation. For illustration purposes, the results of a pilot study are included. The presented study highlights a need for further improvement regarding the predictivity and applicability domain of (Q)SAR systems for pesticides and their metabolites, but also raises other questions such as model selection, establishment of acceptance criteria, harmonised approaches to the combination of model outputs into overall conclusions, adequate reporting and data sharing. © 2020 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.     

硝唑尼特的一般毒性和致突变性研究

通过小鼠经口急性毒性试验、蓄积毒性和耐受性试验研究了硝唑尼特的一般毒性;通过Ames试验、小鼠骨髓细胞微核试验和小鼠精子畸形试验研究了硝唑尼特的致突变性.结果表明:硝唑尼特对小鼠口服LD50为6.295 g/kg,属实际无毒类物质;对小鼠20d给药蓄积系数K＞5.26,属弱蓄积或基本无蓄积毒性,未产生耐受性;对组氨酸缺...     

溴氰菊酯的毒性和致突变性的研究进展

由于高效低毒、对光稳定等优点,溴氰菊酯广泛应用于各类害虫、寄生虫防治中。近年来,溴氰菊酯的毒性、致突变性研究逐渐受到人们的关注。笔者综述了溴氰菊酯的毒性、致突变性研究现状。     

康氏木霉诱变株(NN—15B_7)酶粉的致突变性研究

给小鼠一次口服康氏木霉诱变株(NN—15B_7)粗酶粉,结果LD_(50)>15g/kg体重,属无毒物.Ames试验,康氏木霉纯酶粉3.83～5000μg/皿的5个试验组,对组胺酸缺陷型鼠伤寒沙门氏菌TA_(97) 、TA_(98)、TA_(100)三株菌在加与不加S_9活化系统中,回变菌落数与自发回变菌落数相近,无剂量效应关系.微核试验,用康氏木霉粗酶粉1.25、2.5和5g/kg体重连续2d给小鼠口服,结果各试验组微核率(1.6‰～1.8‰)均在正常范围内,PCE/RBC比值也与阴性对照组无显著差异.精子畸形试验,精子畸形率(1.88%～1.96%)与阴性对照组(1.78%)比较无显著差异,与阳性对照组(8.35%)比较差异非常显著(P<0.01).因此认为,康氏木霉诱变株(NN—15B_7)酶粉无毒性,无致突变性.     

之江菌素对沙门氏菌和小鼠的致突变研究

通过Ames试验、精子畸变试验和微核试验检测之江菌素诱变性.结果表明,用低浓度(0.05 μg/皿)至高浓度(500 μg/皿)6个梯度的之江菌素样品处理后,鼠伤寒沙门氏菌组氨酸营养缺陷型TA97a,TA98,TA100,TA102的回复突变菌落数均未超过其自发回复突变菌落数的两倍;用461.52,230.76,115.38 mg/kg 3个剂量处理ICR雄性小鼠,低、中剂量组精子畸形数与阴性对照组无显著性差异(P>0.05),高剂量组呈显著差异(P<0.05),但无剂量反应关系;576.9,115.38,57.69 mg/kg 3个剂量未能诱发ICR雄性小鼠的微核增加,对细胞分裂亦无明显影响,表明各项试验结果均为阴性.因此在本试验条件下,之江菌素是一种非诱变剂.     

运用RAPD技术检测除草剂对草鱼的致突变作用

用使它隆和嗪草酮注射草鱼，抽取注射前后的草鱼血液提取基因组DNA，选用20个随机引物对草鱼基因组DNA进行RAPD扩增。结果表明，11个引物能产生2～9条扩增带，扩增产物分子大小在200～1900bp之间。其中引物S10能检出用使它隆染毒前后草鱼基因组DNA的差异，引物S17能检出用嗪草酮染毒前后草鱼基因组DNA的差异。RAPD技术可运用于环境水质监测。     

苯甲酸钠对小鼠骨髓细胞的致突变作用研究

采用小鼠骨髓细胞微核试验、小鼠骨髓细胞染色体畸变试验研究了食品防腐剂苯甲酸钠对小鼠骨髓细胞的致突变作用。结果显示:小鼠骨髓细胞微核试验及小鼠骨髓细胞染色体畸变试验均呈阳性(P<0.01),证明苯甲酸钠是染色体断裂剂,而且对雄性动物的致突变作用更大,所引起的染色体结构畸变以染色体断裂为主要类型。     

Synthesis and Biological Evaluation of Novel 3-Alkylpyridine Marine Alkaloid Analogs with Promising Anticancer Activity

Cancer continues to be one of the most important health problems worldwide, and the identification of novel drugs and treatments to address this disease is urgent. During recent years, marine organisms have proven to be a promising source of new compounds with action against tumoral cell lines. Here, we describe the synthesis and anticancer activity of eight new 3-alkylpyridine alkaloid (3-APA) analogs in four steps and with good yields. The key step for the synthesis of these compounds is a Williamson etherification under phase-transfer conditions. We investigated the influence of the length of the alkyl chain attached to position 3 of the pyridine ring on the cytotoxicity of these compounds. Biological assays demonstrated that compounds with an alkyl chain of ten carbon atoms (4c and 5c) were the most active against two tumoral cell lines: RKO-AS-45-1 and HeLa. Micronucleus and TUNEL assays showed that both compounds are mutagenic and induce apoptosis. In addition, Compound 5c altered the cellular actin cytoskeleton in RKO-AS-45-1 cells. The results suggest that Compounds 4c and 5c may be novel prototype anticancer agents.