Chromosome damage in individuals exposed to heavy metals†

Testing the mutagenic activity of environmental pollutants has become an important area of modern environmental science and prophylactic medicine. The most suitable method for short‐term mutagenicity testing on man, at present, are chromosome studies on somatic cells of exposed individuals. Mutation types analyzed by such studies are of high practical relevance as indicator system of genetic damage induced in man under in vivo conditions. A rather large series of such studies has been dedicated to the action of heavy metals on individuals contacted with these metals under therapeutic, ecological or occupational conditions or by intoxication. Lead, cadmium, chromium, nickel, mercury, zinc and other metals as well as their compounds have been under study. Analyses of that kind, of course, are hampered by difficulties with the distinct estimation of the actual load as well as unclear conditions of exposition, e.g. simultaneous exposition to different metals.

Results obtained till now arouse some suspicion of a direct or indirect mutagenic activity in man by certain chromium and platinum compounds, arsenic, mercury, and combinations of lead with other heavy metals (cadmium, zinc, arsenic, antimony, etc.). Life style, above all smoking habits, well may act comutagenic. In most cases, however, mutagenic activity of metals and metal compounds apparently is clearly superposed by their toxic activity. In specific cases, chromosome studies also may contribute to discover sources of ecological exposition and to monitor occupational load by heavy metals.     

DNA damage in mouse organs and in human sperm cells by bisphenol A

Abstract

The in vivo genotoxic potential of bisphenol A using the comet assay in mice and in human sperm cells in vitro without metabolizing enzymes was studied. Male mice were exposed by oral gavage to the following doses of bisphenol A (0 125, 250 and 500?mg/kg body weight). DNA damage was investigated in liver, kidney, testes, urinary bladder, colon and lungs cells. In testicular cells, a significant increase in DNA strand breaks was observed in the lowest, but not in the medium or highest dose groups. Histopathological investigation of the testicular samples did not show any treatment dose-related effects. No DNA strand breaks were observed in any of the other investigated tissues. In human sperm cells in vitro, bisphenol A did not induce DNA strand breaks.     

Alkylation of metals and the activity of metal‐alkyls†

The biochemical basis for resistance to metal ion toxicity is emerging though it is complicated by the different resistance mechanisms. Several strategies for resistance to toxic metal ions have been identified:

1. The development of energy driven efflux pumps which keep toxic element levels low in the interior of the cell. Such mechanisms have been described for Cd(II) and As(V).

2. Oxidation (e.g. AsO^2‐ to AsO₄ ^3‐) or reduction (e.g. Hg²⁺ to Hg⁰) can enzymatically and intracellularly convert a more toxic form of an element to a less toxic form.

3. The biosynthesis of intracellular polymers which serve as traps for the removal of metal ions from solution such as traps have been described for cadmium, calcium, nickel and copper.

4. The binding of metal ions to cell surfaces.

5. The precipitation of insoluble metal complexes (e.g. metal sulfides and metal oxides) at cell surfaces.

6. Biomethylation and transport through cell‐membranes by diffusion controlled processes.

In this short review I shall discuss the implications of biomethylation as a detoxification mechanism for microorganisms as well as for certain higher organisms.     

Sorption,cellular distribution,and cytotoxicity of imidazolium ionic liquids in mammalian cells – influence of lipophilicity

In order to assist an integrated development of ionic liquids (ILs), a study on the sorption, distribution, and cytotoxicity of a series of 1-alkyl-3-methyl imidazolium tetrafluoroborates with C6 rat glioma cells has been performed. Cellular sorption and distribution among three cellular fractions (cytosol, nuclei, and membranes) were analysed by reversed-phase HPLC (RP-HPLC). Compounds with longer 1-alkyl substituents were sorbed with higher enrichment factors and sorption coefficients per protein than those with shorter 1-alkyl chains. The 1-octyl-3-methyl imidazolium cation (C₈MIM) was enriched 17-folds whereas C₆MIM and C₄MIM were enriched by factors of 3.5 and 2.3, respectively. After fractionation of cells by centrifugation, about 8% of C₈MIM was found in the nuclear fractions. The cytotoxicity as estimated by the tetrazolium reductase assay was increasing with the lengths of the 1-alkyl chains from C₄MIM to C₁₀MIM. Consistently, cell proliferation rates were decreasing with increasing lengths of the 1-alkyl chains. The results reveal the correlations between lipophilicity, cellular sorption, and cytotoxicity.     

Cytotoxicity and cell membrane depolarization induced by aluminum oxide nanoparticles in human lung epithelial cells A549

The cytotoxicity of 13 and 22 nm aluminum oxide (Al₂O₃) nanoparticles was investigated in cultured human bronchoalveolar carcinoma-derived cells (A549) and compared with 20 nm CeO₂ and 40 nm TiO₂ nanoparticles as positive and negative control, respectively. Exposure to both Al₂O₃ nanoparticles for 24 h at 10 and 25 µg mL^?1 doses significantly decreased cell viability compared with control. However, the cytotoxicity of 13 and 22 nm Al₂O₃ nanoparticles had no difference at 5–25 µg mL^?1 dose range. The cytotoxicity of both Al₂O₃ nanoparticles were higher than negative control TiO₂ nanoparticles but lower than positive control CeO₂ nanoparticles (TiO₂ < Al₂O₃ < CeO₂). A real-time single cell imaging system was employed to study the cell membrane potential change caused by Al₂O₃ and CeO₂ nanoparticles using a membrane potential sensitive fluorescent probe DiBAC₄(3). Exposure to the 13 nm Al₂O₃ nanoparticles resulted in more significant depolarization than the 30 nm Al₂O₃ particles. On the other hand, the 20 nm CeO₂ particles, the most toxic, caused less significant depolarization than both the 13 and 22 nm Al₂O₃. Factors such as exposure duration, surface chemistry, and other mechanisms may contribute differently between cytotoxicity and membrane depolarization.     

镉对血管内皮细胞损伤及其致动脉硬化的毒理学机制

采用人脐静脉内皮细胞体外培养和大鼠镉染毒实验,检测镉对人脐静脉内皮细胞和大鼠血清NO和ICAM-1分泌量,及大鼠主动脉病理改变的影响。结果表明,镉染毒可造成血管内皮细胞NO分泌量明显降低和ICAM-1分泌量明显升高,与镉染毒浓度剂量相关,体外细胞培养与活体动物实验的结果表现出一致性(P<0.05)。镉暴露可明显促进血管内皮细胞凋亡,主动脉HE染色见动脉硬化改变,各层均见较多ICAM-1阳性表达,主要存在于粥样斑块区。因此,过量镉摄入通过影响大鼠血管内皮细胞功能和结构促进动脉粥样硬化的形成。     

生物样品中含PBDEs在内的复合污染组分的抗雌激素效应

为初步探讨电子废物拆解导致的多溴二苯醚(PBDEs)及其类似物构成的复合污染的潜在生态/健康风险,从电子废物拆解区的三黄鸡血液和肝脏样品中提取了包含PBDEs在内的复合污染组分,分别体外暴露乳腺癌MCF-7细胞和MDA-MB-231细胞6d,检测细胞增殖和雌激素靶基因pS2的mRNA表达.结果表明,包含多种PBDEs在内的复合污染组分在不产生细胞毒性的前提下,可显著抑制MCF-7细胞增殖和雌激素靶基因pS2的mRNA表达,表现出抗雌激素活性.此结果提示由电子废物拆解造成的复合污染对生物体和人体可能存在潜在的生态/健康风险.     

Fate of proteins of waste activated sludge during thermal alkali pretreatment in terms of sludge protein recovery

Maillard reaction between reducing sugars and amides happened during pretreatment. Over 90 min of TAH at the optimal condition, 67.59% sludge proteins was solubilized. 15.84% soluble proteins broke down to materials with small molecular weight. Proteins are the major organic component s of waste activated sludge (WAS); the recovery of sludge proteins is economically valuable. To efficiently recover sludge proteins, WAS should undergo hydrolysis pretreatment to fully release proteins from sludge flocs and microbial cells into aqueous phase. One of the most widely used chemical methods for that is thermal alkali hydrolysis (TAH). Here, the soluble protein concentration achieved the highest level over 90 min of TAH pretreatment at 80°C; the sludge floc disintegration and microbial cell destruction were maximized according to the content profiles of bound extracellular polymeric substance (EPS) and ribonucleic acid (RNA) of sludge. Both less proteins broken down to materials with small molecular weight and less melanoidin generated were responsible. TAH pretreatment at 80°C for 90 min resulted in the solubilization of 67.59% of sludge proteins. 34.64% of solubilized proteins was present in soluble high molecular; 1.55% and 4.85% broke down to polypeptides and amino acids. The lost proteins via being converted to ammonium and nitrate nitrogen accounted for 9.44% of solubilized proteins. It was important to understand the fate of sludge proteins during TAH pretreatment in terms of protein recovery, which would be helpful for designing the downstream protein separation method and its potential application.     

六溴环十二烷(HBCD)对H4细胞和SK-N-AS细胞脱碘酶2和3表达的影响

六溴环十二烷(hexabromocyclododecane,HBCD)与多溴联苯醚(polybrominated diethyl ethers,PBDEs)复合污染体系,对人类健康尤其神经系统所造成的潜在危害及其机制一直是笔者课题组的研究方向。HBCD是广泛使用的溴化阻燃剂,与PBDEs一样,会通过干扰内分泌系统、影响甲状腺激素分泌及损伤神经系统,对生物体产生发育神经毒性。作为系列研究之一,本研究以H4人脑神经胶质瘤细胞和SK-N-AS人神经母细胞瘤细胞为体外生物模型,通过观察HBCD对H4细胞Ⅱ型脱碘酶(Dio2)和SK-N-AS细胞Ⅲ型脱碘酶(Dio3)表达的调控,初步探讨了HBCD对神经系统局部甲状腺激素水平的潜在影响。H4细胞和SK-N-AS细胞分别暴露于0、1、3和9μmol·L-1HBCD 24 h后,采用MTT法检测细胞活力,Western Blot和RT-PCR法分别分析Dio2和Dio3蛋白和基因的表达,酶联免疫吸附测定(ELISA)法检测H4细胞脑源性神经细胞营养因子(BDNF)的分泌。结果表明,HBCD以剂量依赖方式降低H4细胞和SK-N-AS细胞生存率,引起H4细胞Dio2蛋白和基因表达下调,而致SK-N-AS细胞Dio3蛋白和基因表达上调。此外,HBCD还降低H4细胞BDNF的分泌。这表明,HBCD很可能通过影响神经和胶质细胞脱碘酶的表达,影响脑局部甲状腺激素水平,从而引起神经系统损伤及发育神经毒性。     

Enhanced hydrogen production in microbial electrolysis through strategies of carbon recovery from alkaline/thermal treated sludge

• High hydrogen yield is recovered from thermal-alkaline pretreated sludge. • Separating SFL by centrifugation is better than filtration for hydrogen recovery. • The cascaded bioconversion of complex substrates in MECs are studied. • Energy and electron efficiency related to substrate conversion are evaluated. The aim of this study was to investigate the biohydrogen production from thermal (T), alkaline (A) or thermal-alkaline (TA) pretreated sludge fermentation liquid (SFL) in a microbial electrolysis cells (MECs) without buffer addition. Highest hydrogen yield of 36.87±4.36 mgH₂/gVSS (0.026 m³/kg COD) was achieved in TA pretreated SFL separated by centrifugation, which was 5.12, 2.35 and 43.25 times higher than that of individual alkaline, thermal pretreatment and raw sludge, respectively. Separating SFL from sludge by centrifugation eliminated the negative effects of particulate matters, was more conducive for hydrogen production than filtration. The accumulated short chain fatty acid (SCFAs) after pretreatments were the main substrates for MEC hydrogen production. The maximum utilization ratio of acetic acid, propionic acid and n-butyric acid was 93.69%, 90.72% and 91.85%, respectively. These results revealed that pretreated WAS was highly efficient to stimulate the accumulation of SCFAs. And the characteristics and cascade bioconversion of complex substrates were the main factor that determined the energy efficiency and hydrogen conversion rate of MECs.