Relative Genotoxicities of PAH of Molecular Weight 252 AMU in Coal Tar-Contaminated Sediment

Bioassay-directed chemical fractionation methodology was used to calculate relative mutagenic potencies of polycyclic aromatic hydrocarbons (PAH) of molecular weight 252 amu in coal tarcontaminated sediment from Sydney Harbour, Nova Scotia. A normal phase HPLC technique was used to separate organic solvent extracts into fractions containing isomeric PAH of a single benzologue class. Bioassays with Salmonella typhimurium strain YG1025 with the addition of oxidative metabolism (S9) showed that approximately 50% of the mutagenic activity observed in the sediment extract was associated with PAH of molecular weight 252 amu. Further separation of the 252 PAH fraction using reversed phase HPLC yielded subfractions containing individual compounds; bioassay dose-response curves for these subfractions showed that benzo[a]pyrene was responsible for approximately 75% of the activity of the 252 PAH fraction.     

Chlorinated Polycyclic Aromatic Hydrocarbons Associated with Drinking Water Disinfection: Synthesis,Formation under Aqueous Chlorination Conditions and Genotoxic Effects

Polycyclic aromatic hydrocarbons (PAHs) are among the most persistent and toxic organic micropollutants present in water and several of them are mutagenic and carcinogenic. Although it has been shown that chlorinated derivatives of PAHs (Cl-PAHs) may be formed during the water chlorination procedure, little is known about their potential genotoxic and carcinogenic effects. The objectives of the present work were to prepare and characterize the major chlorinated derivatives of benzo[a]pyrene (BaP) and fluoranthene (Fluo), to develop an analytical methodology for their quantification in water samples and to analyse their potential genotoxicity. Chlorinated standards were prepared by a newly developed two phase method (water/n-hexane) using sodium hypochlorite. 6-Chloro-benzo[a]pyrene was selectively obtained from BaP, while 1,3-dichloro-fluoranthene and 3-chloro-fluoranthene were obtained from Fluo. All products were isolated and characterized by nuclear magnetic resonance and mass spectrometry. The formation of BaP- and Fluo-chlorinated derivatives under aqueous chlorination conditions was observed using a SPE-HPLC-FLD methodology. In addition, the cytotoxic and genotoxic activities of the three chlorinated derivatives were analyzed in comparison to their parent compounds, in a human-derived hepatoma cell line using the neutral red uptake and comet assays, respectively. The results showed that, at the equimolar doses of 100 and 125 μM, 6-Cl-BaP was able to induce a significantly higher level of DNA damage than BaP, suggesting a more potent genotoxic effect. In contrast, neither Fluo nor its chlorinated derivatives were genotoxic in the same cell line. The identification of new and possibly hazardous water chlorination by-product from PAHs emphasizes the need to minimize total organic carbon content of raw water and the implementation of safer water disinfection methods.     

有机污染物理化性质与毒理学性质的预测

本文采用分子电性距离矢量（MEDV）分别表征了多种有机污染物的分子结构,应用多元线性回归（MLR）技术,同时采用逐步回归结合统计检测对模型变量进行筛选,分别建立了有机污染物的沸点和急性毒性与MEDV的定量结构-性质关系（QSPR）模型。继用留一法和外部样本对模型稳定性能进行检验。结果表明：所建QSPR模型有良好的稳定性和预测能力,该研究结果为预测有机污染物的理化性质和毒理学性质提供了的理论依据。     

Hemocompatibility,cytotoxicity, and genotoxicity of poly(methylmethacrylate)/nanohydroxyapatite nanocomposites synthesized by melt blending method

The aim of this study was to show the hemocompatibility, cytotoxicity, and genotoxicity of nanocomposites that were synthesized with different molecular weights of poly(methyl methacrylate) (PMMA) and different concentrations of nanohydroxyapatite (nHAp). Different techniques to characterize the nanocomposites were used. The cytotoxicity and genotoxic effects of the polymers and nanocomposites on human lymphocytes were determined by acid phosphatase assay, viability test, and comet assay. Moreover, hemocompatibility test was performed. It was found that all of the PMMA/nHAp nanocomposites are highly hemocompatible and biocompatible, none of the nanocomposites showed a cytotoxic effect, and nHAp addition decreased the genotoxicity.     

Abnormal chromosome assessment of snakehead fish (Channa striata) affected by heavy metals from a reservoir near an industrial factory

This study aimed to investigate nine heavy metal concentrations (As, Cd, Cr, Pb, Cu, Fe, Zn, Mn and Ni) in water, sediment and snakehead fish (Channa striata) and to identify abnormal chromosomes in C. striata from a reservoir near an industrial factory and a reference area. Heavy metal concentrations were measured by inductively coupled plasma optical emission spectrometry (ICP-OES). The metal concentrations in the water, sediment and C. striata samples did not exceed the standard limit of Thailand, except for Cr concentrations, which exceeded water quality standards. The concentrations of Cd, Fe, Mn and Ni in C. striata samples between the reservoir and the reference area were significantly different (p < 0.05). The diploid chromosome number of C. striata from both areas was (2n = 42). Eight types of abnormal chromosomes were identified and classified as a single-chromatid gap, a single-chromatid break, centric fragmentation, a centric gap (CG), fragmentation, deletion, single-chromatid decomposition and iso-arm fragmentation. The most frequent abnormal chromosome in the samples was CG. The percentages of abnormal chromosomes in the C. striata samples from the reservoir near the industrial factory and the reference area were significantly different (p < 0.05) at 8.44 and 1.20, respectively.     

阿斯巴甜和糖精的基因毒性体外测试研究

目的 阿斯巴甜和糖精作为人工合成甜味剂的代表,其安全性问题一直备受争议,被认为有致癌风险但缺乏充分科学证据,需进一步研究考证。方法 基于课题组前期建立的DNA损伤及致癌性体外定量评估方法,采用液相色谱串联质谱技术(Liquid Chromatography-Tandem Mass Spectrometry,LC-MS/MS)定量检测阿斯巴甜和糖精两种甜味剂急性或亚急性暴露细胞后生成的基因损伤生物标志物γ-H2AX和p-H3;另采用高内涵筛选技术(High Content Screening,HCS)检测暴露后细胞中与DNA损伤修复途径相关的四种重要生物标志物即γ-H2AX、p-H3、Rad51和p53 的表达水平,并考察其量效和时效关系。结果 LC-MS/MS检测结果表明阿斯巴甜和糖精在考察浓度下均不会引起细胞γ-H2AX和p-H3表达增加,即未呈现染色体断裂和纺锤体毒性;HCS检测结果显示糖精对四种生物标志物均无影响,阿斯巴甜对p53、γ-H2AX和p-H3三种DNA损伤生物标志物无明显影响,但引起DNA同源重组修复(Homologous Recombination Repair, HRR)蛋白Rad51呈现无剂量依赖性的显著增加。结论 本研究表明阿斯巴甜和糖精经两种基因毒性体外测试方法检测,均未呈现显著基因毒性。     

紫色杆菌素及脱氧紫色杆菌素的基因毒性评价

目的：考察紫色杆菌素、脱氧紫色杆菌素以及二者混合物的基因毒性,为其更广泛的活性研究和应用奠定基础。方法：利用SOS/umu检测试剂盒定量分析紫色杆菌素、脱氧紫色杆菌素、二者混合物以及各自的S9代谢产物是否刺激鼠伤寒沙门菌Salmonella typhimurium NM2009细胞产生了SOS修复,以及与阳性药物2-氨基芴（2-aminofluorene,AF-2）和2-氨基蒽（2-aminoanthracene,2-AA）进行对比所产生毒性作用的强弱。结果：32.6 μg/mL的脱氧紫色杆菌素、经S9代谢后的34.2 μg/mL的紫色杆菌素和33.4 μg/mL的混合物对S. typhimurium NM2009细胞产生了基因毒性,但与阳性对照物相比属于低毒性物质,且相同剂量的紫色杆菌素和脱氧紫色杆菌素以及二者混合物的基因毒性基本相同,二者混合后未产生协同效应。结论：紫色杆菌素和脱氧紫色杆菌素属于低基因毒性物质。