2—硝基芴的致突变性受共存多环芳烃的影响

本文以Ａｍｅｓ试验的ＴＡ９８菌株研究了２－硝基芴在其它多环芳烃共存时，其致突变性的变化，结果显示：它与其它硝基多环芳烃共存时，直接致突变性增强；而与其它无直接致突变性的多环芳烃共存时，其直接致突变性减弱，且多环芳烃的环数越多，减弱作用越强，这强能是因为硝基多环芳烃具有亲电子性，ＤＮＡ的碱基有亲核性，易于结合，造成ＤＮＡ的损伤；而多环芳烃是一般具有供电子性，阻碍了硝基多环芳烃与ＤＮＡ碱基的结合。     

彗星试验检测区域水源有机污染致突变量(Study on Mutagenic Threshold of Organic Pollutants in Typical Water Area by Comet Assay)

采用彗星试验检测了区域水源有机污染对人血淋巴细胞的致突变性,探讨了水源风险的评价方法.结果表明:Cr(VI)对人外周血淋巴细胞有强的致突变作用,并具有明显的剂量-效应关系;Cr(VI)剂量的对数与人外周血淋巴细胞DNA损伤的程度呈线性相关.可以用Cr(VI)作为阳性参照物量化表征水中有机污染混合物对人血淋巴细胞的致突变性.现行《地表水环境质量标准》、《污水综合排放标准》中Cr(VI)的限值可以用于评价水体中有机污染对人体健康的风险.     

农药麦病治的毒性研究

本文报道麦病治的毒理研究结果。急性毒性试验表明，麦病治为低毒物质，蓄积毒性试验Ｋ〉５，为弱蓄积性，体外致突变试验结果表明，麦病治无致基因突变作用，体内细胞水平试验未见到有致骨髓嗜多染红细胞微核率升高的作用，生殖系统致突变试验表明，麦病治不会导致生殖细胞的染色体损伤，对ＳＤ系大鼠的生殖能力及胎鼠的生长发育均未见不良影响，对胎鼠外观，骨骼内脏无致畸作用。     

农药麦病治的毒性研究

本文报道麦病治的毒理研究结果。急性毒性试验表明，麦病治为低毒物质，蓄积毒性试验Ｋ＞５，为弱蓄积性。体外致突变试验结果表明，麦病治无致基因突变作用。体内细胞水平试验未见到有致骨髓嗜多染红细胞微核率升高的作用。生殖系统致突变试验表明，麦病治不会导致生殖细胞的染色体损伤，对ＳＤ系大鼠的生殖能力及胎鼠的生长发育均未见不良影响，对胎鼠外观、骨骼内脏无致畸作用。     

硝基多环芳烃——环境中最近发现的直接致突变物和潜在致癌物

大气及其他污染源颗粒物的直接致突变性 1977年Talcott与wei及Pitts等利用短期生物试验Ames试验研究了美国城市的大气颗粒物,发现颗粒物中除有需用肝酶(S-9)活化的致突变物、以苯并(a)茈为代表的多环芳烃(PAH)外,还包含有一类过去没有人注意到的“直接致突变物(direct-acting mutagens)”,后者与PAH不同,无需添加S-9就能显示致突变活性。图     

2-硝基芴的致突变性受共存多环芳烃的影响

本文以Ames试验的TA_(98)菌株研究了2-硝基芴(2-Nitroflurene)在其它多环芳烃共存时,其致突变性的变化.结果显示:它与其它硝基多环芳烃共存时.直接致突变性增强;而与其它无直接致突变性的多环芳烃共存时,其直接致突变性减弱,且多环芳烃的环数越多、减弱作用越强,这可能是因为硝基多环芳烃具有亲电子性,DNA的碱基有亲核性,易于结合,造成DNA的损伤;而多环芳烃一般具有供电子性,阻碍了硝基多环芳烃与DNA碱基的结合.     

工业碳黑的致突变性研究

本文研究了工业碳黑有机溶剂萃取物的致突变性.发现其萃取物在Ames试验中显示极强的直接致突变性,特别是经过硝化工艺的碳黑.而且萃取溶剂不同,其致突变性也不同,以氯苯和二氯甲烷为溶剂的萃取物活性较高.经进一步分析测定,在萃取物中含有二硝基芘和3-硝基芴酮等硝基多环芳烃,前者是一种非常强的直接致突变物,它们是工业碳黑致突变性的主要供献者,光照可以降低碳黑萃取物的致突变活性.     

二氧化氯和液氯消毒饮用水致突变性的比较

本文运用国内外广泛应用的Ａｍｅｓ试验,对二氧化氯与液氯消毒水样进行了致突变性的比较,结果表明,ＣｌＯ２消毒的水样未显示出致突变性,而液氯消毒的水样显示致突变性的研究结果为ＣｌＯ２在饮用水消毒中的应用提供了科学的依据。     

采用生物发光检测法进行Ames试验的研究

将自行构建的含有青海弧菌荧光酶基因的质粒pACYCL184引入Ames试验的4个菌株TA97、TA98、TA100、TA102中,构建成能够生物发光的工程菌,分别命名为TAL97、TAL98、TAL100、TAL102.实验表明,该4株工程菌保持原出发菌株所具有的与Ames试验相关的性状,对各类致突变剂有良好的反应,且可用平皿计数法进行致突变试验.其发光值与致突变剂浓度存在良好的量效关系,故可用发光检测取代原Ames试验的平皿计数,使检测更简单、方便、快速.图3表3参11     

复方阿苯达唑/伊维菌素及其单药的体内外致突变性研究

农业生产上常用的阿苯达唑和伊维菌素均有一定的致突变性。为了解伊维菌素和阿苯达唑按1:24形成固定剂量复方的致突变性,以及复方和单药致突变性的差异,采用Ames试验、小鼠骨髓微核试验和小鼠精子畸变试验进行复方阿苯达唑/伊维菌素及其单药的致突变性研究。结果表明,复方阿苯达唑/伊维菌素能提高小鼠骨髓嗜多染红细胞的微核率和精子畸形率,但在单复方的比较中发现,单药的微核率和精子畸形率均高于复方,表明复方毒性有所降低。同时,无论是复方还是单药均不能提高组氨酸缺陷型沙门氏菌的突变率。以上表明,虽然复方阿苯达唑/伊维菌素致突变毒性低于单药,但仍然是一种能引起小鼠骨髓微核率和精子畸形率升高的致突变阳性药物,因此需警惕该药物的食品残留问题及对生态环境的危害。     

生物样品体外致突变高通量检测方法研究进展

评述了几种常用的体外致突变检测方法及其用于生物样品检测的可行性,有些方法经改进可用于高通量检测生物样品体外致突变性.经典Ames实验受生物样品中组氨酸的影响,易产生假阳性结果,尽管经过修正可以排除组氨酸的干扰,但操作繁琐,不适合高通量检测.基于SOS反应的检测体系避开了组氨酸的影响,且简单易行,适合高通量检测:以β-半乳糖苷酶基因(lacZ)作为报告基因的检测体系灵敏度高,且经过离心洗涤或后培养的方式可降低样品颜色的影响;以绿色荧光蛋白(GFP)基因作为报告基因的检测体系避开了颜色的干扰,但这类方法灵敏度普遍不高,可以寻找信号更强的荧光蛋白以替代GFP;荧光素酶(lux)基因集lacZ和GFP的优点于一身,但检测时需要额外添加辅助因子,限制了其应用.也对单细胞凝胶电泳、tk基因突变实验、染色体损伤检测等方法进行了分析,有些适合生物样品高通量检测,但由于缺少国际通用的标准,很难推广使用.     

Dose-response relationships in mutagenicity assays including an appropriate positive control group: a multiple testing approach

The objective of mutagenicity assays in regulatory toxicology is the decision on non-mutagenicity or mutagenicity. An inherent problem of statistical tests is the possibility of false decisions, i.e., a mutagenic substance will be falsely labeled as non-mutagenic or a non-mutagenic substance will be falsely labeled as mutagenic. These probabilities of false negative (consumer's risk=type II error) and/or false positive decision (producer's risk=type I error) can be limited by using suitable testing procedures as well as a design including an appropriate positive control. Using the proof of hazard concept the well-known many-to-one procedures with total order restriction for increasing effect differences are used, while using the proof of safety concept procedures on equivalence with total order restriction are discussed. Both approaches are demonstrated on a real data example.     

Assessment of mutagenic potency of source water treated by ozone and adsorption processes

This research utilized the Ames test to determine the mutagenicity of water treated by advanced processes, including ozonation and granular activated carbon (GAC). Raw water samples for this research included those obtained from the Pan Hsin waterworks as well as samples containing humic acids. Treated samples were collected from the pilot‐scale advanced treatment plant. The Ames test was used to measure the mutagenicity of the water after each treatment process. For the Pan Hsin raw water samples treated with ozone or GAC, it was indicated that, regardless of whether samples were preozonated or not, they all showed a mutagenic potency less than 2 once the S9 enzyme was added. This level of mutagenicity is insignificant. The prepared humic acid samples, on the other hand, demonstrated a significant reduction in mutagenicity after the pre‐ozonation process, indicating that preozonation can lower the degree of mutagenicity. Furthermore, the mutagenicity of the prepared humic acid samples gradually decreased after the advanced treatment process. However, when chlorine was added later to these samples, the mutagenicity increased again. This research shows that the use of O3/GAC processes to treat water can successfully lower mutagenicity, indicating a great potential for applications in the treatment of drinking water.     

A model based on molecular structure descriptors for predicting mutagenicity of organic compounds

A model predictive of the potential mutagenicity of organic compounds was devised by relating mutagenicity data obtained in the Ames reversion test to molecular structure parameters describing their hydrophobic, topological, steric and electronic properties. These included second order valence molecular connectivity index, parachor, molar refraction and polarizability of electrons. A classification rule was calculated, by means of discriminant analysis, using a training set of 117 compounds of various chemical classes. There was agreement between experimental data and theoretical expectations for the majority of compounds (70.9%), with homogeneous figures among the different chemical classes under scrutiny. An exception was represented by halogenated aliphatics with up to 3 C atoms, the mutagenicity of which was poorly predicted by the structural analysis model.     

Ames测试不确定性分析

Ames测试具有实验周期短、简便的优点,是目前普遍采用的检测化合物致突变性的初筛方法,但Ames测试仍有一定的不确定性.本文主要依据本实验室的研究结果分析了Ames测试中测试菌株、统计回复子数目的时间及2倍判定标准给测试结果带来的不确定性,对影响Ames测试结论存在假阳性及假阴性的因素做了进一步分析与讨论.图6表1参19     

共存氯代酚结构对1-NP致突变性的影响

研究了氯代酚与1－NP的单一和联合致突变效应,结果发现,各氯代酚对1－NP的致突变性有不同程度的抑制作用,且抑制效应系数（S）与各氯代酚的分子描述参数的关系能用QSAR方程表示,由方程得出的预测值与实验测定值之间能较好地吻合。     

Analyses of PAHs (polycyclic aromatic hydrocarbons) and mutagenicity in raw and chlorinated water

Both raw water and chlorinated drinking water samples were collected from and the Liu‐Du water treatment plant in northern Taiwan from October 1990 to April 1992. The polycyclic aromatic hydrocarbons (PAHs) and mutagenicity in these water samples were analyzed by GC/MS and Ames test. The Mutagenicity/DMSO (Dimethyl Sulfoxide) ratio in S. typhimurium TA98 and TA100 with or without S9 mixture increased, even higher than 2, following the sequence of unit process. It was observed that the mutagenicity with TA98 (S9+) was highly related to most of PAHs in the raw water; while the mutagenicity with TA98 (S9+) was only correlated with DbA and BghiPr in the treated water. It could be expected that the mutagenicity level was controlled by other predominant components after the raw water was treated, for example, the chlorination process.     

Testicular DNA synthesis inhibition—an in vivo system for the detection of mutagenic and carcinogenic chemicals

By binding covalently to DNA chemical mutagens and carcinogens inhibit replication, which can be measured as a decrease in thymidine incorporation into DNA. This DNA synthesis inhibition (DSI) has been determined in testicular cells of mice for a large number of compounds and has been found to correlate very well with their known mutagenic and carcinogenic properties.

Not only could this test give a qualitative answer about potential carcinogenicity or mutagenicity, but, with regard to its in vivo characteristics, could furthermore give an indication of the carcinogenic and mutagenic potency and thus be of use in the risk evaluation of chemical substances; the relationship between the DNA synthesis inhibition and the underlying alkylation of guanine ‐0⁶ by different methylating agents is demonstrated.

As toxic effects decrease thymidine incorporation, too, means are discussed for distinguishing between “true”;, mutagenic, and “false”;, cytotoxic, DNA synthesis inhibition.

In conclusion, the implications of including the DSI‐test in a battery of mutagenicity tests are outlined.