The cytotoxicity of nici2 for mammalian cells in culture†

The effects of NiCl₂ were studied in two human cell lines, HeLa and diploid embryonic fibroblasts as well as in V79 Chinese hamster cells and in L‐A mouse fibroblasts. NiCl₂ produces a dose‐dependent depression of proliferation, mitotic rate, and viability, accompanied by an increasing release of lactic dehydrogenase and stimulation of lactic acid production. The plating efficiency is reduced, as are DNA and protein synthesis and, to a lesser degree, RNA synthesis.

The cytotoxicity of NiCl₂ is comparable in degree to those of PbCl₂ and MnCl₂, but is weaker than those of HgCl₂ and CdCl₂. However, the different sensitivities of different cell lines must also be considered.

NiCl₂ effects are more severe in serum‐free medium than in medium containing serum or serum albumin indicating that serum constituents, notably albumin, bind the metal effectively and inhibit cellular uptake; this confirms earlier reports on the serum binding and slow uptake of NiCl₂.

Synchronized cells are most sensitive in the Gl and early S phases of the cell cycle. In the Painter test the depression of DNA synthesis persists following cessation of exposure to NiCI₂. These findings contribute an explanation for the known genotoxic effects of nickel.     

Biochemical properties of beryllium potentially relevant to its carcinogenicity†

The carcinogenicity of beryllium to several animal species is well established and evidence exists which strongly suggests that this is the case in human exposure. In this review several biochemical properties of the metallocarcinogen are considered including, the causation of cell transformation, and infidelity of DNA synthesis, inhibition of cell division and enzyme induction, and interference with regulatory mechanisms controlling gene expression. These effects are discussed in relation to beryllium chemistry, cellular accumulation mechanisms and distribution to subcellular organdies and molecular targets. It is suggested that the ultimate location and interactions of the metal ion in cell nuclei and its selective inhibition of certain protein phosphorylation reactions in particular are the biochemical effects potentially most relevant to induction of beryllium carcinogenesis.     

Uptake and genotoxicity of micromolar concentrations of cobalt chloride in mammalian cells

Literature data concerning the genotoxicity of cobalt salts have been conflicting. To establish appropriate incubation conditions, we conducted a series of uptake studies, before genotoxicity was determined by DNA strand break induction in HeLa cells and mutagenicity in V79 Chinese hamster cells. Co(II) is taken up by HeLa cells in a concentration‐dependent manner and is accumulated inside the cell. The uptake is preceded by a fast association step to the outer membrane, with no saturation up to 24 h. DNA strand breaks as determined by nucleoid sedimentation are induced at concentrations as low as 50μMCoCl₂. The induction is time‐dependent, showing the highest number of breaks after 4h incubation with no further increase up to 24h. CoCl₂ is mutagenic at the HPRT‐locus, enhancing the spontaneous mutation frequency 4.2‐fold at 100μ?. Besides direct interactions with DNA, the mutagenicity of CoCl₂ could also be due to a decrease in the Fidelity of DNA polymerisation.     

Biochemical speciation in chromium genotoxicity

The biochemical speciation of chromium compounds in mammalian cells is discussed with respect to uptake, metabolism, DNA binding and damaging. Whereas soluble hexavalent chromium is taken up rapidly and accumulated intracellularly after its reduction, compounds of trivalent chromium penetrate biomembranes about three orders of magnitude slower. Cr(VI) after its uptake is metabolised by electron donating compounds via Cr(V) to Cr(III) compounds. Chromium from various Cr(III) compounds, but not chromate, binds to chromatin in isolated cell nuclei. The DNA‐protein crosslinks and DNA strand breaks observed in rat liver and kidney after chromate administration are also found in vitro, when Cr(III) compounds (but not chromate) interacts with isolated nuclei. In the Chinese Hamster cell HGPRT mutation assay, three out of four tested Cr(III) complexes were found to be mutagenic. In a direct DNA strand break assay with supercoiled bacteriophage PM 2 DNA, neither chromate nor the four Cr(III) compounds tested caused nicks. However, the combined action of chromate plus glutathione as well as the isolated complex of pentavalent chromium, Na₄Cr(glutathione)₄, did cause DNA breaks. Reactive oxygen species are inferred to be the ultimate DNA nicking agents in this assay. In conclusion there appear to be two mechanisms of chromate genotoxicity; one with direct DNA damage caused by Cr(V) species and one via DNA‐protein crosslinks formed with Cr(III), the final reduction state of chromate.     

Genetic toxicology of metal compounds: An examination of appropriate cellular models †

Bacterial systems have not had success predicting metal carcinogenicity. Hypotheses explaining this failure are examined. Using a broad genetic endpoint, λ prophage induction, under sub‐toxic growing conditions, genotoxicity is seen for compounds of chromium, manganese, lead, molybdenum and tungsten. Copper, manganese, arsenic and molybdenum compounds enhanced UV mutagenesis in E. coli WP2.

The toxicity of metal compounds to cultured mammalian cells correlates well with rat oral LD₅₀ values. Whereas insolubility can present problems in bacterial studies, concentrations of metal compounds toxic to mammalian cells can be determined even in the presence of precipitate, and sometimes [Pb(NO₃)₂, BaCl₂ and BeCl₂] occurs only in its presence. PbS and MnS, which are insoluble, are much more toxic than the more soluble compounds Pb(NO₃)₂ and MnCl₂. These results demonstrate the importance of cellular phagocytosis of insoluble metal compounds as a factor in studying the toxicity and genotoxicity of metal compounds.     

喹啉为MFC阳极燃料的微生物群落结构演化分析

通过构建填料型微生物燃料电池(MFC),首次对以喹啉为燃料时的MFC阳极表面的微生物群落进行了分析.PCR-DGGE的试验结果表明,随着燃料的改变,微生物群落也发生改变.当以喹啉和葡萄糖的混合溶液稳定地作为燃料时,由于受到喹啉毒性的抑制,微生物多样性降低,优势菌也发生明显的改变.与葡萄糖共基质相比,以单一喹啉为燃料时的阳极微生物优势菌落发生明显改变.新增加一类菌,这类菌与Pseudomonas sp. DIC5RS 的同源性为100%,推测该菌在单一喹啉为MFC燃料时喹啉的降解过程中起到关键作用.     

珠江口海域3种重要有害藻类的溶血毒性研究

从珠江口海域分离、鉴定出3种重要有害藻类小普林藻JX12(Prymnesium parvum)、剧毒卡尔藻JX24(Karlodinium veneficum)、红色赤潮藻JX14(Akashiwo sanguinea),在实验室条件下研究了不同反应温度和pH值对小普林藻溶血活性的影响,在此基础上对海洋微藻溶血活性的测定方法进行了优化,并进一步分析比较了不同藻株以及不同生长时期溶血毒性的变化特征。研究结果显示,在实验温度范围内(4~50°C),小普林藻的溶血活性随温度的升高而增大,37℃为其最佳反应温度,pH 8和50 min为其最佳反应条件。不同生长时期的小普林藻溶血毒性具有显著差异,对数期溶血活性(5.67×10~(-7)HU·cell~(-1))显著高于稳定期(2.32×10~(-7)HU·cell~(-1))和衰亡期(3.40×10~(-7)HU·cell~(-1))。分离自珠江口海域的3种微藻均检测出溶血毒性,单个细胞溶血活性由强到弱分别为红色赤潮藻(976.20×10~(-7)HU·cell~(-1))、小普林藻(5.67×10~(-7)HU·cell~(-1))、剧毒卡尔藻(2.58×10~(-7)HU·cell~(-1))。值得注意的是,红色赤潮藻中国株JX14的单位细胞溶血活性显著高于美国株AS2,是后者的2倍以上。本研究首次确认珠江口海域红色赤潮藻、小普林藻和剧毒卡尔藻均具有较强的溶血毒性,这些有害藻类一旦形成赤潮可能对河口生态系统安全以及水产养殖业造成严重危害。     

大气细颗粒物对小鼠T淋巴细胞亚群的影响

大气颗粒物对肺免疫系统有潜在毒性作用,打破免疫系统平衡,大气颗粒物成分中危害首当其冲的是大气细颗粒物(PM_(2.5)),为研究大气细颗粒物引起的机体T淋巴细胞中Th1/Th2免疫失衡方向。本研究通过免疫组化实验方法检测暴露后小鼠肺组织中T淋巴细胞的表达,进一步采用流式细胞术检测大气细颗粒物气管滴注后小鼠肺脏淋巴细胞中Th1/Th2比例。暴露组小鼠肺组织免疫组化研究结果提示浸润细胞区有大量的CD4~+T细胞,中高剂量暴露组小鼠肺组织中淋巴细胞亚群Th1/Th2比例向Th1偏移。大气细颗粒物影响免疫失衡,使T淋巴细胞向Th1漂移。     

四氯联苯对鸡外源原始生殖细胞迁移的影响

为了研究环境污染物四氯联苯对移植的原始生殖细胞增殖性迁移的影响,将发育至14期的供体鸡胚原始生殖细胞用PKH26荧光染料标记,然后移植到经过四氯联苯处理的受体鸡胚生殖新月区域,继续孵化,检测其迁移和增殖情况.结果表明,和对照组相比,四氯联苯可明显降低移植原始生殖细胞在血液和性腺中的数量;四氯联苯对外源性原始生殖细胞迁移有明显影响,但雌二醇对外源性原始生殖细胞的增殖性迁移无明显影响,揭示四氯联苯可能影响的是受体性腺的诱引物质,且这种影响是非雌激素样的作用.     

电化学氧化杀灭水库原水中藻类的研究

由Ti/RuO2棒为阳极、不锈钢管为阴极组成电氧化管式反应装置,对电氧化杀灭水库含藻原水中的藻类进行了研究。结果显示:处理累积停留时间20 min后,叶绿素a去除率达100%,对浓缩10倍水样,藻毒素MCLR的去除率达98%以上。细胞的死亡及胞内物质的损失,导致溶液DOC值从32 mg/L上升至50 mg/L,但在电氧化作用下,可下降至12 mg/L。氧化降解产物使溶液UV254值上升,从0.09 cm-1上升至0.14 cm-1,溶液UV410值没有太大变化。处理过程中pH值从8.4迅速下降至7.4后,基本维持稳定,电导率以21μS/(cm.min)速率呈线性下降趋势,溶液离子浓度改变较大。