THE STUDY FOR MUTAGENIC TOXICITY OF DIMEHYPO

利用生物微核测定技术，检测了杀虫双对几种水生脊椎动物的微核及核异常效应。结果表明：阳性对照药物丝裂霉素Ｃ对鲢鱼红细胞的微核率有显著影响，且有明显的剂量—效应关系。农药杀虫双对两栖类蝌蚪、鲢鱼及鲤鱼红细胞的微核率没有显著影响。但能显著地诱导蝌蚪及鲤鱼红细胞核异常的产生。说明杀虫是一种非致突变物，但它对各种水生脊椎动物红细胞核膜有一定损伤作用。     

杀虫双致突变性研究

利用生物微核测定技术，检测了杀虫对对几种水生脊椎动物的微核及核异常效应，结果表明：阳性对照药物丝裂霉素Ｃ地链鱼红细胞的微核率有显著影响，且有明显的剂量－效应关系，农药杀虫双对两栖类蝌蚪，链鱼及锂鱼红细胞的微核率没有显著影响，但能显著地诱导蝌蚪及锂鱼红细胞核异常的产生，说明杀虫是一种非致突变物，但它对各种水生脊椎动物红细胞核膜有一定损伤作用。     

体外人淋巴细胞核异常测试法检测间接诱变剂环磷酰胺的研究

用间接诱变剂环磷酰胺（ＣＰ）对人体外全血淋巴核细胞核异常测试法进行了验证研究，实验结果表示，ＣＰ可诱发各项核损伤指标的增量，即微核率（ＭＮＦ），核变形率（ＩＮＦ），核破裂率（ＫＮＦ）等，并且与测量呈正相关，其中以综合核损伤指标核异常率（ＮＡＦ）为优，ＭＮＦ和ＩＮＦ次之，表明该方法不失为一种快速简便，稳定的哺乳动物体外测试方法，可用于化学诱变剂遗传毒性的评价，但应根据测试化学品合理选用核异常指标的组     

5种物质对除草剂精克草星诱发黄鳝外周血红细胞微核和核异常的抑制作用

以外周血红细胞微核率和核异常细胞率为指标,研究了５种物质对除草剂精克草星的诱发黄鳝遗传物质损伤的抑制作用。结果表明,维生素Ｂ２、维生素Ｃ、β－胡萝卜素、生姜和大蒜与精克草星共同作用时,均能显著降低精克草星诱发的微核率及核异常细胞率。说明,这５种物质可降低除草剂精克草星对鱼类的遗传毒性,对鱼类具有保护作用。另外,还对这５种物质抑制作用的机理进行了讨论。     

5种物质对除草剂精克草星诱发黄鳝外周血红细胞微核和核异常？…

以外周血红细胞微核率和核异常细胞率为指标,研究了５种物质对除草剂精克草星的诱发黄鳝遗传物质损伤的抑制作用。结果表明,维生素Ｂ２、维生素Ｃ、β－胡萝卜素、生姜和大蒜与精克草星共同作用时,均能显著降低精克草星诱发的微核率及核异常细胞率,说明,这５种物质可降低除草剂精克剂精克草星对鱼类的遗传毒性,对鱼类具有保护作用,另外,还对５种物质抑制机理进行了讨论     

体外人全血淋巴细胞核异常检测的研究

应用不同类型的具有致癌、致突变作用的治疗因子:丝裂霉素C、噻替哌、乙双吗啉、γ线(0.5-5Gy)和中子束(5-40Gy)体外处理人全血,观察多种核损伤指标:微核、核变形、核裂解、核固缩及其复合指标——核异常的改变。结果多数核损伤指标呈现剂量依赖关系。尽管多种核损伤指标对不同治疗因子的反应有所差异,但检测化学诱变剂的敏感性以微核细胞率为优,其次为核裂解率,其它指标有参考价值,对不同剂量区放射线处理后,核损伤指标的剂量效应关系的研究,将有助于体外生物剂量仪的探讨,尤其对超量照射(>5Gy)的研究。认为,体外人全血淋巴细胞核异常检测作为一种简便、快速、较接近人体内情况、且较敏感的体外遗传毒理学方法,可试用于理化因子诱变性与潜在致癌性的评价。     

微核率在放射治疗中的研究进展

微核是由于各种物理化学因素导致细胞染色体发生断裂后 ,细胞进入下一次分裂时 ,染色体片段不能随有丝分裂进入子细胞核 ,在细胞浆中形成直径 <1/3主核 ,完全与主核分开的圆形或椭圆形微小核。其嗜色与主核一致 ,是染色体畸变在间期核中所表现出的一种损伤类型 ,它是反映染色体稳定性的可靠的生物学标志之一 ,与染色体畸变的其他检测结果基本一致。微核率 (micronucleusfrequency ,MNF)测定是一种简便快速的细胞遗传学检查方法 ,计数微核率可以反映致畸因素对细胞的损伤程度。放射后的细胞染色体断裂、分裂异常 ,导致微核形成[1] ,下面就…     

汞、铅对小鼠睾丸和生殖细胞的亚慢性毒性

背景与目的: 研究重金属汞、铅对雄性小鼠睾丸和附睾精子的亚慢性毒性作用及其对生精细胞的遗传损伤。材料与方法:分别用高中低3种浓度氯化汞、醋酸铅经腹腔染毒4周龄雄性ICR小鼠,共10次,之后自由饲养23 d,于第50 d观察睾丸指数、附睾精子数量、精子活动率和精子头畸形率以及生精细胞微核率和减数分裂异常率。结果: 高浓度醋酸铅组小鼠睾丸指数低于对照组。中、高浓度氯化汞组、3种浓度醋酸铅组附睾精子密度低于对照组。中、高浓度醋酸铅组附睾精子活动率低于对照组。3种浓度氯化汞、醋酸铅致附睾精子畸形率升高。高浓度醋酸铅组生精细胞微核率高于对照组,3种浓度氯化汞和低、中浓度醋酸铅生精细胞微核率与对照组相比差异无显著性。各处理组减数分裂异常率与对照组差异均无显著性。 结论: 汞、铅暴露对小鼠精子具有亚慢性毒性作用,高浓度铅组影响生精细胞的微核率。     

双核淋巴细胞微核细胞率检测的方法学初探

双核淋巴细胞微核细胞率检测的方法学初探高广花，徐厚恩，郝卫东北京医科大学卫生毒理教研室１０００８３胞质分裂阻断法计数双核细胞中的微核细胞率，这是一种较新的微核分析方法，本文对其检测的敏感性及表达遗传损伤的可恢复性进行了初步的研究。材料和方法１．现场及...     

水环境致突变物生物监测的研究——鱼类外周血红细胞微核检测敏感性比较

本文报道了用9种淡水养殖鱼类进行水环境污染物致突变敏感性试验结果,观察的定量指标是外周血细胞的微核率．核异常率等,试验结果表明,鲫鱼,黄鳝,泥鳅为敏感品种,其中鲫鱼是水环境中低浓度污染物长时间致突变性检验的好材料,其敏感指标是微核率,黄鳝的敏感指标是核异常率,泥鳅的敏感指标是核异常率和巨核细胞率;     

脑星形细胞瘤形态计量病理分级诊断的研究

目的:探讨星形细胞瘤形态定量病理分级诊断方法。方法:应用图像分析定量技术,对136例人星形细胞瘤和3例正常对照的细胞核的面积等8项形态参数、肿瘤4项分布密度参数和细胞核分维值进行量化。结果:经图像分析定量,说明细胞核的面积、周长、直径、短轴和长轴、细胞核数、巨细胞面数密度、血管交点面数密度和细胞核面数密度等9项指标能够较好地反映星形细胞瘤4级间的差异,具有较好的鉴别诊断价值。结论:应用形态计量方法进行星形细胞瘤的病理分级诊断更加客观可靠。     

乳腺癌细胞核形态的分形分析

本文在肿瘤细胞核形态的研究中引入分形论，选择临床上常见的乳腺癌，在电镜下观察肿瘤细胞核的形态，通过分形图象处理系统，采用数盒子的方法计算细胞核边界的分维值，结果的统计采用t检验在EPI－5统计软件上进行．结果发现．乳腺癌和乳腺纤维腺瘤的细胞核边界的分维值大于其拓维值1（P＜0．01），即它们是分形结构．乳腺癌细胞核边界的分维是1．166±0．045，大于乳腺纤维腺瘤细胞核边界分维1．065±0．022（P＜0．00001）．上述研究表明：在电镜观察下（放大倍数5000～12000倍）肿瘤细胞核的形态具有分形结构；分维定量地描述了肿瘤细胞核形态的不规则程度，对肿瘤病理良恶性的鉴别具有一定意义．     

肺癌细胞核形态的分形分析

目的在肿瘤细胞核形态的研究中引入分形论。方法选择肺癌标本１１例，在电镜下观察肿瘤细胞核的形态，通过分形图象处理系统，用数盒子的方法计算细胞核边界的分维值，并用ｔ检验在ＥＰＩ－５统计软件进行结果统计。结果肺癌细胞和支气管粘膜上皮细胞核边界的分维值大于其拓扑维值１（Ｐ＜０．０１），即它们是分形结构。肺癌细胞核边界的分维是１．１８３±０．０５４，大于支气管粘膜上皮细胞核的边界分维１．０５８±０．０１８（Ｐ＜０．００００１）。结论电镜下（放大倍数５０００～１２０００倍）肿瘤细胞核形态具有分形结构；分维定量地描述了肿瘤细胞核形态的不规则程度，对良恶性肿瘤的鉴别具有一定意义。     

A genetic defect in exportin-5 traps precursor microRNAs in the nucleus of cancer cells

The global impairment of mature microRNAs (miRNAs) is emerging as a common feature of human tumors. One interesting scenario is that defects in the nuclear export of precursor miRNAs (pre-miRNAs) might occur in transformed cells. Exportin 5 (XPO5) mediates pre-miRNA nuclear export and herein we demonstrate the presence of XPO5-inactivating mutations in a subset of human tumors with microsatellite instability. The XPO5 genetic defect traps pre-miRNAs in the nucleus, reduces miRNA processing, and diminishes miRNA-target inhibition. The XPO5 mutant form lacks a C-terminal region that contributes to the formation of the pre-miRNA/XPO5/Ran-GTP ternary complex and pre-miRNAs accumulate in the nucleus. Most importantly, the restoration of XPO5 functions reverses the impaired export of pre-miRNAs and has tumor-suppressor features.     

Solution conformation and mutagenic specificity of 1,N6-ethenoadenine

Site-specific studies in several laboratories established that each of the three etheno adducts, 1,N6-ethenoadenine (epsilon A), 3,N4-ethenocytosine (epsilon C) and N2,3-ethenoguanine (N2,3-epsilon G), is mutagenic. In Escherichia coli, epsilon A is only weakly mutagenic in single-stranded DNA (mutation frequency, 0.1%), and epsilon C is at least 20 times more mutagenic than epsilon A. Prior treatment of host cells with ultraviolet irradiation enhances the mutagenic frequency of epsilon C by 30-60%, even when the E. coli is recA. Likewise, enhanced mutagenicity was observed when the host cells lacked 3'-->5' exonuclease activity of DNA polymerase III. epsilon A induces all three base substitutions, but A-->G predominates. epsilon C induces epsilon C-->T and epsilon C-->A substitutions, but only the latter was enhanced after ultraviolet irradiation of host cells. In contrast to the results in bacteria, both epsilon A and epsilon C are potent mutagenic lesions in simian kidney cells, inducing 70 and 81% base substitutions, respectively. In simian kidney cells, epsilon A exclusively induces epsilon A-->G transitions, whereas epsilon C-->A transversions are the major type of mutation induced by epsilon C. Nuclear magnetic resonance (NMR) spectrometry of the four possible pairs containing epsilon C indicated that both epsilon C:G and epsilon C:T pairs are stabilized by hydrogen bonds. Even though the latter forms the most stable pair containing epsilon C, the etheno adduct is in syn alignment. DNA polymerase appears to continue DNA synthesis with a syn-orientated base only in the absence of proofreading exonuclease activity or when ultraviolet irradiation-inducible proteins are present. For epsilon A, only epsilon A:T and epsilon A:G pairs have been studied by NMR, which showed that the former has no hydrogen bond whereas the latter maintains two hydrogen bonds with the etheno base in syn orientation. Determination of the relationship between a particular conformation of epsilon A and its mutagenic activity must await further studies. In a site-specific study of epsilon A with human cell extracts, an 11-mer oligonuclotide with a single epsilon A was inserted into an M13 bacteriophage containing an SV40 origin of replication. This vector was replicated in vitro with human fibroblast cell extracts, and the replicated products were analysed. In this experiment, epsilon A induced predominantly epsilon A-->G transitions but at a mutation frequency of 0.14%.     

用微核法观察硒对环磷酰胺致突变活性的影响

以微核(MN)试验和淋巴细胞非特异性酸性萘酯酶(ANAE)染色法观察了不同浓度亚硒酸钠溶液对环磷酰胺(CP)致突变作用及对小鼠免疫细胞活性的影响。结果表明0.005％和0.001％二种浓度的亚硒酸钠溶液作用于小鼠,可降低由CP所致的骨髓细胞微核形成率升高,并增强和稳定了其外周血淋巴细胞ANAE的活性。提示,合适浓度的硒有稳定机体免疫功能,拮抗CP的致突变作用。     

7种农药对植物及人外周淋巴细胞SCE影响的比较观察

目的：研究杀虫磺、杀虫双、杀虫环、杀菌剂NF133、蚓哚乙酸、久效磷和氧化乐果7种农药对人和植物细胞染色体的诱变性,并比较其诱变作用在人和植物上是否一致。方法：测定蚕豆、大麦根尖细胞和人外周血淋巴细胞姐妹染色单体交换（SCE）率。结果：7种农药都能明显诱导蚕豆、大麦根尖细胞和人外周血淋巴细胞和SCE率增加。结论：本研究中7种农药对植物和人细胞均有较强的作用。对植物细胞与对人细胞的诱变作用是一致的。     

Mutational specificity of the anti 1,2-dihydrodiol 3,4-epoxide of 5-methylchrysene

An SV40-based pS189 shuttle vector, which contained a supF target gene and was replicated in human cells (Ad293), was used to determine the mutational specificity of anti 5-methylchrysene 1,2-dihydrodiol 3,4-epoxide, the active metabolite of the environmentally prevalent carcinogen 5-methylchrysene. The frequency of supF mutants containing point mutations increased with dose to approximately 40 times the spontaneous frequency. The induced mutations were not randomly distributed but occurred preferentially at mutagenic hotspots, which were not all identical to those reported by others for benzo[a]pyrene dihydrodiol epoxide, a metabolite with similar chemistry.     

p53 Mutations are present in colorectal cancer with cytoplasmic p53 accumulation

Previous studies have shown that nuclear p53 over-expression is an indicator of p53 mutations whereas cytoplasmic p53 accumulation is related to wild-type p53 in several kinds of tumors. Cytoplasmic p53 accumulation has been demonstrated to be an independent prognostic factor in colorectal adenocarcinomas. The purpose was to examine whether mutations occur in cases with p53 accumulated in the cytoplasm and whether there are any differences in the frequency and characteristics of p53 mutations in different staining patterns. In the present study, we identified p53 mutations using PCR single-strand conformation polymorphism (SSCP) and DNA sequencing in 75 primary colorectal adenocarcinomas with different staining patterns (negative, nucleus, cytoplasm, nucleus and cytoplasm). The results show that the frequency and nature of mutations in tumors with cytoplasmic p53 accumulation were similar to those with nuclear p53 expression. However, the tumors with accumulation in both the nucleus and cytoplasm demonstrated a higher mutation rate. We suppose that the role of cytoplasmic p53 accumulation in predicting prognosis in patients with colorectal cancer may be dependent on both mutational and non-mutational mechanisms.