智力低下儿的细胞微核检查分析

目的探讨染色体异常和细胞微核发生与智力低下的关系。方法选择40例行遗传咨询患儿作为智力低下组,20例正常儿童作为正常对照组,应用常规法分别制备智力低下儿和正常儿童的淋巴细胞及其染色体G显带的标本,检测2组核型和细胞微核率。结果 40例智力低下儿中,共检出15例染色体异常核型,检出率为37.5%,其中21-三体综合征10例（25.0%）;其微核发生率为12.5%,正常对照组染色体异常1例（5.0%）,微核率为3.26%。2组染色体异常发生率和微核率比较,差异有统计学意义（P〈0.01）。结论染色体畸变与微核的形成是引起智力低下发生的重要遗传学原因。     

In vitro genotoxic and cytotoxic effects of some paraben esters on human peripheral lymphocytes

Parabens (PBs) are p-hydroxybenzoic acid ester compounds commonly employed as antimicrobial preservatives, mainly in food, cosmetic, and pharmaceutical products. The aim of the present study was to investigate the genotoxic and cytotoxic effects of some paraben esters (butyl paraben, propyl paraben, isobutyl paraben, and isopropyl paraben) on human peripheral lymphocytes, using in vitro sister chromatid exchange (SCE), chromosome aberration (CA), and cytokinesis-block micronucleus (CBMN) tests. Lymphocyte cultures were treated with four concentrations of PBs (100, 50, 25 and 10?µg/mL) for 24 and 48?h. Paraben esters significantly induced MN formations as compared to solvent control. Furthermore, butyl paraben and propyl paraben increased MN formations a concentration-dependent manner at 24 and 48?h. PBs increased the CA at 24 and 48?h. However, this increase was not meaningful for butyl paraben and isopropyl paraben at 48?h when compared with solvent control. Butyl, isobutyl, and isopropyl paraben significantly increased the SCE at 24 and 48?h. However, propyl paraben did not induce SCE meaningfully in both treatment periods. A significant decrease in the cytokinesis-block proliferation index and mitotic index was observed in cells exposed to all concentrations of PBs at 24 and 48?h. However, proliferation index was not affected at all concentrations of PBs after 24?h treatment, although it was decreased at the highest concentration of PBs at 48?h. It is concluded that all of the paraben esters used in this study have highly genotoxic and cytotoxic effects on human lymphocytes cells in vitro.     

Co-assessment of cell cycle and micronucleus frequencies demonstrates the influence of serum on the in vitro genotoxic response to amorphous monodisperse silica nanoparticles of varying sizes

Serum proteins have been shown to modulate the cytotoxic and genotoxic responses to nanomaterials. The aim was to investigate the influence of serum on the induction of micronuclei (MN) by nanoparticles (NPs) of different sizes. Therefore, A549 human lung carcinoma cells and amorphous monodisperse silica nanoparticles (SNPs) were used as models. Assessment of the cell viability, cell cycle changes and induction of MN by SNPs ranging from 12 to 174 nm was performed in presence or absence of serum, applying the in vitro flow cytometry-based MN assay. Here, it has been demonstrated that serum has an influence on these end points, with a lower cell viability in absence of serum compared with the presence of serum. Further, cell cycle changes, specifically, G₁ and S-phase arrest, were observed in absence of serum for four out of six SNPs tested. A size-dependent MN induction was observed: larger SNPs being more active in absence of serum. In addition, the serum influence was characterised by a size-dependency for cytotoxic and genotoxic effects, with a higher influence of serum for smaller particles. The data indicate that the in vitro micronucleus assay in presence and absence of serum could be advised for hazard assessment because it demonstrates a higher sensitivity in serum-free conditions than in conditions with serum. However, this recommendation applies only if the cell line used is able to proliferate under serum-free conditions because cell division is a prerequisite for MN expression.     

Evaluation of Cytotoxicity,Genotoxicity and Hematotoxicity of the Recombinant Spore-Crystal Complexes Cry1Ia,Cry10Aa and Cry1Ba6 from Bacillus thuringiensis in Swiss Mice

The insecticidal properties of Cry-endotoxins from Bacillus thuringiensis (Bt) have long been used as spore-crystals in commercial spray formulations for insect control. Recently, some Bt-endotoxin genes have been cloned in many different plants. Toxicological evaluations of three spore-crystal endotoxins, BtCry1Ia, BtCry10Aa and BtCry1Ba6 from B. thuringiensis, were carried out on mice to understand their adverse effects on hematological systems and on genetic material. These three spore-crystals have shown toxic activity to the boll weevil, which is one of the most aggressive pests of the cotton crop. Cry1Ia, Cry10Aa and Cry1Ba6 did not increase the micronucleus frequency in the peripheral erythrocytes of mice and did not cause changes in the frequency of polychromatic erythrocytes. However, some hematologic disburbances were observed, specifically related to Cry1Ia and Cry1Ba6, respectively, for the erythroid and lymphoid lineage. Thus, although the profile of such adverse side effects can be related to their high level of exposure, which is not commonly found in the environment, results showed that these Bt spore-crystals were not harmless to mice, indicating that each spore-crystal endotoxin presents a characteristic profile of toxicity and might be investigated individually.     

Genotoxicity and cytotoxicity of sevoflurane in two human cell lines in vitro with ionizing radiation

Objective:

To determine the in vitro toxicity of different concentrations of sevoflurane in cells exposed to X-ray.

Methods:

The genotoxic effects of sevofluorane were studied by means of the micronucleus test in cytokinesis-blocked cells of irradiated human lymphocytes. Subsequently, its cytotoxic effects on PNT2 (normal prostate) cells was determined using the cell viability test (MTT) and compared with those induced by different doses of X-rays.

Results:

A dose- and time-dependent cytotoxic effect of sevofluorane on PNT2 cells was determined (p >0.001) and a dose-dependent genotoxic effect of sevofluorane was established (p >0.001). Hovewer, at volumes lower than 30 μL of sevofluorane at 100%, a non-toxic effect on PNT2 cells was shown.

Conclusion:

Sevofluorane demonstrates a genotoxic capacity as determined in vitro by micronucleus test in cytokinesis-blocked cells of irradiated human lymphocytes.     

Relevance of microscopic indicators of chromosomal instability in routine reporting of malignancies

Chromosomal instability (CIN) is the defining feature of most human cancers. The role of CIN has been suggested in diagnosis and prognostication of the tumors since long. However, the molecular methods used for its identification are costly, require expertise and may not be available in many of the laboratories. Therefore, this article tries to revisit the already described morphological indicators of CIN like multipolar mitoses, chromatin bridges, chromatin strings, nuclear heterogeneity, laggards, nuclear buds, micronuclei, and multinucleated micronucleated cells. The role of above as morphological biomarkers in diagnosis and prognosis of various cancers has been reviewed and the possibility of their inclusion in day to day reporting of malignancies is also discussed. Diagn. Cytopathol. 2014;42: 181–188. © 2013 Wiley Periodicals, Inc.     

实验性氟中毒小鼠微核率的研究

目的 探讨高氟对小鼠微核率的影响。方法 实验组小鼠饮用不同浓度的含氟水,对照组小鼠饮用正常自来水,比较两组小鼠的微核率,用χ＾２检验方法作显性检验。结果 实验组中饮用高氟水小鼠的微核率明显高于对照组,有显性差异（Ｐ〈０．０５）;小鼠微核率与饮水含氟量有明显相关性（Ｐ〈０．０５）。结论 高氟可增高小鼠骨髓嗜多染红细胞的微核率,说明高氟对小鼠的染色体有损伤作用,高氟可能是致突变物。     

骨髓增生异常综合征患者外周血淋巴细胞微核观察

观察25例骨髓增生异常综合征(MDS)和30例正常人外周血淋巴细胞微核。MDS患者外周血微核淋巴细胞出现率为84.00%,淋巴细胞微核率为6.68‰,显著高于对照组(P<0.005)。RAEB和RAEB-T亚型淋巴细胞微核率显著高于RA亚型(P<0.005)。MDS微核淋巴细胞多微核率与对照组差异无显著性(P>0.05)。同时检查外周血淋巴细胞染色体,MDS染色体畸变率为14.68%,显著高于对照组,且与微核率呈直线正相关(r=0.76,P0.001)。本文就MDS微核检测的意义进行了讨论。     

全血培养胞质分裂阻断微核(CBMN)实验方法的改进

 目的  改良全血培养胞质分裂阻断微核(cytokinesis-block micronucleus,CBMN)实验制片法及探讨细胞松弛素B(cytochalasin B,cyt-B)的最佳浓度。方法  依据常规微核试验制片法,在低渗液的温度、固定液比例和操作手法等方面改进实验方法;设置不同浓度cyt B组(4、5、6、7 μg/mL),常规外周血淋巴培养至44 h加入cyt-B,继续培养至68 h或72 h,收获细胞。按人类微核计划(HUMN Project)中的识别标准识别双核、多核细胞和微核(micronuclei,MN),确定cyt B最适浓度,并分析cyt-B对自发微核率的影响。结果  改良法所获的双核淋巴细胞的胞膜完整,边界清晰,微核易于辨认。培养72 h后,cyt B浓度≥5 μg /mL时,双核细胞比例较4 μg /mL 组显著增加(P=0.001);cyt-B浓度≥6 μg/mL时,三核以上细胞比例显著增加(P=0.01)。培养68 h后,cyt-B浓度为6 μg/mL时,双核细胞比例较高(58.4%)。各浓度组淋巴细胞自发微核率的差异无统计学意义(P=0.32)。结论  改良法选用cyt-B浓度为5 μg/mL、培养72 h或cyt-B浓度为6 μg/mL、培养68 h时收获的细胞,可获得大量双核细胞,且胞膜完整,染色清晰;cyt-B对淋巴细胞自发微核率无显著影响。     

秦皮总香豆素致突变作用研究

目的评价秦皮总香豆素的致突变性。方法应用Ames试验、小鼠骨髓微核试验对秦皮总香豆素进行了致突变研究。结果秦皮总香豆素在受试剂量40～20000μg/皿范围内,各剂量组各菌株与阴性对照组比较均未见回变菌落数明显增加。秦皮总香豆素三个试验剂量组微核率均在正常范围内,经卡方检验与阴性对照组比较无显著性差异(P>0.05)。结论本实验条件下秦皮总香豆素无致突变作用。