Wentilactone A的遗传毒性评价

目的 检测Wentilactone A的遗传毒性。方法 应用经典遗传毒性检测组合(Ames试验、体外培养CHO细胞染色体畸变试验和小鼠骨髓微核试验)检测Wentilactone A的遗传毒性。结果 Ames试验结果提示,Wentilactone A在每皿5 000、500、50、5、0.5 μg 5个剂量下,在加和不加代谢活化系统（S9）时,对鼠伤寒沙门菌均无致突变性。CHO细胞染色体畸变试验结果提示,在终浓度23.74、47.48、94.96 μg/ml 3个剂量组,在加和不加S9中,于作用4 h和24 h的条件下培养的CHO细胞,均未诱发染色体畸变。小鼠骨髓微核试验在100、200、400 mg/kg 3个剂量下作用24 h以及400 mg/kg剂量下作用48 h对骨髓细胞的微核诱发率,与溶剂对照组比较均无显著差异（P>0.05）。结论 Wentilactone A对鼠伤寒沙门菌无致突变性,对CHO细胞的染色体无致畸变作用,对ICR小鼠无诱发骨髓细胞微核的效应。上述结果提示Wentilactone A不具有遗传毒性和潜在致癌性。     

鸡蛋花提取物的抗突变活性研究

目的 探讨鸡蛋花提取物是否具有抗突变活性,为其开发应用提供实验依据.方法 采用高内涵体外微核实验和Ames实验,计数微核细胞数、回复突变菌落数,计算微核细胞率、相对菌落数及其抑制率;评价不同浓度的鸡蛋花提取物的抗突变效应.结果 高内涵体外微核实验中鸡蛋花提取物20、10mg/mL 2个剂量预处理致突变剂条件下的微核细胞率与致突变剂对照组比较差异有统计学意义(P＜0.01);鸡蛋花提取物与致突变剂同时加入条件下未观察到抗突变效应.Ames实验中鸡蛋花提取物预处理致突变剂条件下对TA98、TA100的相对回变菌落数与致突变剂对照组比较差异有统计学意义(P＜0.01或P＜0.05),且呈一定的剂量-反应关系;同时加入条件下只在25 mg/皿剂量组呈现出对致突变剂的抑制作用.结论 本实验条件下,鸡蛋花提取物能够直接灭活致突变剂,具有一定的拮抗突变的作用.     

In vitro genotoxic and cytotoxic effects of doxepin and escitalopram on human peripheral lymphocytes

Antidepressants are drugs used for the treatment of many psychiatric conditions including depression. There are findings suggesting that these drugs might have genotoxic, carcinogenic, and/or mutagenic effects. Therefore, the present in vitro study is intended to investigate potential genotoxic and cytotoxic effects of the antidepressants escitalopram (selective serotonin reuptake inhibitor) and doxepin (Tricyclic antidepressant) on human peripheral lymphocytes cytokinesis-block micronucleus (CBMN), sister chromatid exchange (SCE), and single cell gel electrophoresis (alkaline comet assay) were used for the purpose of the study. In the study, four different concentrations of both drugs (1, 2.5, 5, and 10?µg/mL) were administered to human peripheral lymphocytes for 24?h. The tested concentrations of both drugs were found to exhibit no cytotoxic and mitotic inhibitory effects. SCE increase caused by 5 and 10?µg/mL of escitalopram was found statistically significant, while no statistically significant increase was observed in DNA damage and micronucleus (MN) formation. Moreover, the increase caused by doxepin in MN formation was not found statistically significant. Besides, 10?µg/mL of doxepin was demonstrated to significantly increase arbitrary unit and SCE formation. These findings suggest that the investigated concentrations of escitalopram and doxepin were non-cytotoxic but potentially genotoxic at higher concentrations.     

Combinations of genotoxic tests for the evaluation of group 1 IARC carcinogens

Many of the known human carcinogens are potent genotoxins that are efficiently detected as carcinogens in human populations but certain types of compounds such as immunosuppressants, sex hormones, etc. act via non‐genotoxic mechanism. The absence of genotoxicity and the diversity of modes of action of non‐genotoxic carcinogens make predicting their carcinogenic potential extremely challenging. There is evidence that combinations of different short‐term tests provide a better and efficient prediction of human genotoxic and non‐genotoxic carcinogens. The purpose of this study is to summarize the in vivo and in vitro comet assay (CMT) results of group 1 carcinogens selected from the International Agency for Research on Cancer and to discuss the utility of the comet assay along with other genotoxic assays such as Ames, in vivo micronucleus (MN), and in vivo chromosomal aberration (CA) test. Of the 62 agents for which valid genotoxic data were available, 38 of 61 (62.3%) were Ames test positive, 42 of 60 (70%) were in vivo MN test positive and 36 of 45 (80%) were positive for the in vivo CA test. Higher sensitivity was seen in in vivo CMT (90%) and in vitro CMT (86.9%) assay. Combination of two tests has greater sensitivity than individual tests: in vivo MN + in vivo CA (88.6%); in vivo MN + in vivo CMT (92.5%); and in vivo MN + in vitro CMT (95.6%). Combinations of in vivo or in vitro CMT with other tests provided better sensitivity. In vivo CMT in combination with in vivo CA provided the highest sensitivity (96.7%).     

网吧环境和槟榔致口腔颊黏膜细胞DNA损伤研究

目的 研究网吧环境和槟榔对口腔颊黏膜细胞DNA的损伤。方法 通过系统抽样抽取长沙市岳麓区5家网吧,在网吧内及网吧所在社区通过单纯随机抽样的方法选取无吸烟、饮酒等习惯的18~40岁健康男性,分别作为对照组(n=50)、网吧上网组(n=41)、咀嚼槟榔组(n=47)、网吧上网且咀嚼槟榔组(n=58)。收集受试者口腔颊黏膜细胞标本,采用单细胞凝胶电泳(single cell gel electrophoresis, SCGE)及颊细胞微核试验(buccal micronucleus cytome, BMCyt)检测DNA损伤情况。结果 网吧上网组和咀嚼槟榔组较对照组SCGE尾部DNA百分含量(%Tail DNA)及BMCyt微核频率(‰MN)显著增高(P＜0.05)。网吧上网且咀嚼槟榔组较网吧上网组和咀嚼槟榔组%Tail DNA及‰MN均显著增高(P＜0.05)。DNA损伤程度与网吧上网累积时间和槟榔咀嚼量呈剂量效应关系。结论 网吧环境和槟榔可分别导致口腔颊黏膜细胞DNA损伤,两者同时暴露会进一步增加DNA损伤程度。     

Chlorpyrifos‐based insecticides induced genotoxic and cytotoxic effects in the ten spotted live‐bearer fish,Cnesterodon decemmaculatus (Jenyns, 1842)

Mortality, genotoxicity, and cytotoxicity of the 48% chlorpyrifos (CPF)‐based formulations Lorsban* 48E^® and CPF Zamba^® were evaluated on Cnesterodon decemmaculatus (Jenyns, 1842) (Pisces, Poeciliidae) under laboratory conditions. Induction of micronucleus (MN) and alterations in the erythrocyte/erythroblast frequencies were employed as end points for genotoxicity and cytotoxicity, respectively. For Lorsban* 48E^®, mean values of 0.13 and 0.03 mg/L were determined for LC₅₀ at 24 and 96 h, respectively, and these concentrations reached mean values of 0.40 and 0.21 mg/L for CPF Zamba^®. Mortality values increased as a positive linear function of the CPF Zamba^® concentrations, but not for Lorsban* 48E^® concentrations. There was no significant relationship between mortality and exposure time within the 0–96 h period for both formulations. LC₅₀ values indicated that the fish were seven fold more sensitive to Lorsban* 48E^® than to CPF Zamba^®. Lorsban* 48E^® within the concentration range of 0.008–0.025 mg/L increased MN frequency at both 48 and 96 h of treatment. Similar results were also observed when fish were exposed to 0.052–0.155 mg/L of CPF Zamba^®, regardless of the exposure time. Cellular cytotoxicity was found after Lorsban* 48E^® and CPF Zamba^® treatments for all concentrations and time exposures, estimated by a decrease in the frequency of mature erythrocytes and a concomitant enhanced frequency of erythroblasts in circulating blood. Furthermore, our results demonstrated that Lorsban* 48E^® and CPF Zamba^® should be considered as CPF‐based commercial formulations with marked genotoxic and cytotoxic properties. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1390–1398, 2014.     

In vitro investigation of the genotoxic and cytotoxic effects of thiacloprid in cultured human peripheral blood lymphocytes

Thiacloprid, a neonicotinoid insecticide, is widely used for controlling various species of pests on many crops. The potential genotoxic effects of thiacloprid on human peripheral blood lymphocytes (PBLs) were investigated in vitro by the chromosome aberrations (CAs), sister chromatid exchanges (SCEs), and cytokinesis‐block micronucleus (MN) assays. The human PBLs were treated with 75, 150, and 300 μg/mL thiacloprid in the absence and presence of an exogenous metabolic activator (S9 mix). Thiacloprid increased the CAs and SCEs significantly at all concentrations (75, 150, and 300 μg/mL) both in the absence and presence of the S9 mix and induced a significant increase in MN and nucleoplasmic bridge formations at all concentrations for 24 h and at 75 and 150 μg/mL for 48‐h treatment periods in the absence of the S9 mix; and at all concentrations in the presence of the S9 mix when compared with the control and solvent control. Thiacloprid was also found to significantly induce nuclear bud (NBUD) formation at 300 μg/mL for 24 h and at 150 μg/mL for 48‐h treatment times in the absence of the S9 mix and at the two highest concentrations (150 and 300 μg/mL) in the presence of the S9 mix. Thiacloprid significantly decreased the mitotic index, proliferation index, and nuclear division index for all concentrations both in the absence and presence of the S9 mix. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 631–641, 2014.     

Investigation of the in vitro toxicological properties of the synthetic cannabimimetic drug CP-47,497-C8

Cannabicyclohexanol (CP-47,497-C8) is a representative of a group of cannabimimetic cyclohexylphenols which is added to herbal mixtures as a cannabis substitute since 2008. Although in the beginning CP-47,497-C8 was the main ingredient of “Spice” and similar products, it was partly replaced by aminoalkylindole-type cannabinoid receptor agonists like JWH-018, JWH-073 or JWH-250, but never completely disappeared from the market. Since information on its toxicological properties is scarce, we investigated the effects of the drug in human derived cell lines. The cytotoxic effects were studied in a panel of assays (SRB, XTT, LDHe and NR tests) in a buccal derived (TR146) and a liver derived (HepG2) cell line. The strongest effects were seen in the two former assays at levels ≥ 7.5 μM indicating that the compound interferes with protein synthesis and causes membrane damage. In additional comet assays, DNA damage was detected at levels ≥ 10 μM. Experiments with lesion specific enzymes showed that these effects are not due to oxidative damage of DNA bases. The negative findings obtained in Salmonella/microsome assays and the positive results of micronucleus tests with the cell lines indicate that the compound does not cause gene mutations but acts on the chromosomal level. In contrast to other synthetic cannabinoids, no indication for estrogenic/antiestrogenic properties was seen in a luciferase assay with bone marrow derived U2-OS cells. In conclusion, our findings show that the drug has only weak cytotoxic properties. However, the induction of chromosomal damage indicates that it may cause adverse effects in users due to its impact on the stability of the genetic material.     

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.