Induction of chromosmal aberrations in the syrian hamster by insecticides tested in vivo

The insecticides demeton, dimetoat, dichlorovos, endosulfan, trichlorofon, carbaryl, lindane, methoxychlor, propoxur and malathion were examined for their ability to induce chromosomal aberrations in the bone marrow cells of the Syrian hamster (Mesocricetus auratus) treated in vivo. Mutagenicity of commercial preparations was examined at four doses: LD₅₀; 1/2, 1/5 and 1/10 LD₅₀. The positive control was an IP injection of cyclophosphamide to hamsters at a dose of 40 mg/kg body wt. Demeton, dichlorovos and endosulfan gave positive results. Malathion, dimethoate and the mixture of methoxychlor and propoxur were weakly clastogenic; at some doses these compounds induced statistically significant increases in the number of aberrations. Trichlorfon and the mixture of carbaryl and lindane were negative in this test.This work was supported by the Polish Academy of Sciences within the projet 09.7.3.4.3     

中孕期胎儿染色体异常高危孕妇羊水细胞胎儿染色体核型及介入性产前诊断指征的大样本分析

目的探讨中孕期胎儿染色体异常(FCA)高危孕妇羊水细胞胎儿染色体核型(FK)及其介入性产前诊断(IPD)指征。方法选择2014—2018年,在四川大学华西第二医院产前诊断中心进行羊膜腔穿刺术羊水细胞FK检测的63581例FCA高危孕妇(孕龄为19~27+6孕周)为研究对象。回顾性分析孕妇不同IPD指征及其胎儿染色体核型异常(FKA)检测结果。本研究遵循的程序符合四川大学华西第二医院伦理委员会所制定的伦理学标准,并通过该伦理委员会批准[审批文号:医学科研2019伦审批第(077)号]。结果①本组63581例中孕期孕妇的FKA检出率为3.13%(1989/63581)。这63581例孕妇的IPD指征分别为高龄(预产期年龄≥35岁)(25648例)、血清学筛查高风险(29009例)、无创产前筛查(NIPT)高风险(333例)、夫妇一方为染色体异常携带者(603例)、超声筛查发现胎儿结构异常及超声软指标异常(2647例)、异常儿生育史(1546例)、于外院进行羊水细胞FK分析结果异常者(7例)、孕妇智力低下及合并智力低下家族史(149例)、孕妇早孕期有害物质接触史(1400例)、其他(2239例),FKA检出率分别为3.26%(836/25648)、2.04%(593/29009)、65.17%(217/333)、34.33%(207/603)、3.51%(93/2647)、1.68%(26/1546)、85.71%(6/7)、4.03%(6/149)、0.14%(2/1400)、0.13%(3/2239)。②351例孕妇的IPD指征为超声筛查发现胎儿结构异常中,IPD指征为胎儿淋巴水囊瘤、皮肤水肿的FKA检出率最高,为26.09%(6/23)。2296例孕妇的IPD指征为胎儿超声软指标异常中,IPD指征为胎儿颈项透明层(NT)值≥2.5 mm的FKA检出率最高,为7.74%(66/853)。结论孕妇高龄、血清学筛查高风险、NIPT高风险、夫妇一方为染色体异常携带者、超声筛查发现胎儿结构异常及超声软指标异常等,均为中孕期孕妇FCA的IPD指征,孕妇IPD指征类型不同,FCA风险不同。羊膜腔穿刺术羊水细胞FK检测,可预测有IPD指征孕妇的妊娠结局,为降低FKA出生率提供参考。     

Role of chromosomal imbalances in the pathogenesis of DSD: A retrospective analysis of 115 prenatal samples

Differences of sex development (DSDs) are a group of congenital conditions characterized by a discrepancy between chromosomal, gonadal, and genital sex development of an individual, with significant impact on medical, psychological and reproductive life. The genetic heterogeneity of DSDs complicates the diagnosis and almost half of the patients remains undiagnosed. In this context, chromosomal imbalances in syndromic DSD patients may help to identify new genes implicated in DSDs. In this study, we aimed at describing the burden of chromosomal imbalances including submicroscopic ones (copy number variants or CNVs) in a cohort of prenatal syndromic DSD patients, and review their role in DSDs. Our patients carried at least one pathogenic or likely pathogenic chromosomal imbalance/CNV or low-level mosaicism for aneuploidy. Almost half of the cases resulted from an unbalanced chromosomal rearrangement. Chromosome 9p/q, 4p/q, 3q and 11q anomalies were more frequently observed. Review of the literature confirmed the causative role of CNVs in DSDs, either in disruption of known DSD-causing genes (SOX9, NR0B1, NR5A1, AR, ATRX, …) or as a tool to suspect new genes in DSDs (HOXD cluster, ADCY2, EMX2, CAMK1D, …). Recurrent CNVs of regulatory elements without coding sequence content (i.e. duplications/deletions upstream of SOX3 or SOX9) confirm detection of CNVs as a mean to explore our non-coding genome. Thus, CNV detection remains a powerful tool to explore undiagnosed DSDs, either through routine techniques or through emerging technologies such as long-read whole genome sequencing or optical genome mapping.     

电离辐射对放射工作者职业健康的影响

目的 分析放射工作者外周血象、淋巴细胞微核及染色体畸变情况,为放射工作者职业防护和健康监测提供依据。方法 对2015年、2017年和2019年连续3次接受健康检查的127名放射工作者进行淋巴细胞微核、染色体及血象分析,将其设为放射组。另外选取133名无射线接触史的医务人员设为对照组;结果 放射组中淋巴细胞微核率和染色体畸变率高于对照组,白细胞和血小板计数低于对照组,均具有统计学意义（P < 0.05）。127名放射工作者外周血白细胞总数随着接触电离辐射时间的增长逐渐降低,染色体畸变率逐渐增加,均具有统计学意义（P < 0.05）。损害工龄大于20年的放射工作者染色体畸变率高于低工龄组,不同损害工龄之间比较无统计学意义（P > 0.05）。核医学与介入治疗工种染色体畸变率高于其他工种,具有统计学意义（P < 0.05）。结论 长时间接触低剂量电离辐射可使放射工作者白细胞总数降低和淋巴细胞染色体畸变率增加,应加强放射工作者防护措施以备降低电离辐射损伤程度,特别要加强核医学和介入治疗放射工作人员的职业防护。     

Analysis of types of chromosomal aberrations following the combined action of chemical mutagens

Types of chromosomal aberrations in cultures of human lymphocytes exposed to the combined action of various concentrations of thiophosphamide and dipin, with different proportions of each, were studied. The mutagens acted on the G₀ stage. The range of concentrations used was from 3.17·10^–5 to 22.19·10^–5M. Equimolar concentrations of thiophosphamide inhibited more chromatid exchanges and fewer sister-strand (isolocus) unions than dipin, and it also induced a greater proportion of single breaks and a greater proportion of breaks in chromatid exchanges relative to the total number of chromosome breaks. Both the absolute and the relative frequencies of chromosomal aberrations depended on the concentration of the mutagens. A change in the ratio between thiophosphamide and dipin, if the total number of molecules of the two mutagens at the different concentration levels remained constant, gave rise to an effect whose level was between the effects of action of equimolar concentrations of the pure mutagens. This effect depended on the proportion of each mutagen in the combined treatment. It is concluded that the action of thiophosphamide and dipin is additive.Laboratory of Mutagenesis, Institute of Medical Genetics, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. V. Smol'yannikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 1, pp. 79–81, January, 1978.     

Molecular cytogenetic characterization of 16p11.2 microdeletions with diverse prenatal phenotypes: Four cases report and literature review

ObjectiveChromosome 16p11.2 deletions have been recognized as a genetic disorder with well-described postnatal phenotypes. However, the prenatal manifestations are atypical for lacking of enough evidence.Case reportFour pregnant women underwent amniocentesis for cytogenetic analysis and chromosomal microarray analysis (CMA) because of various indications for prenatal diagnosis: prenatal ultrasound abnormalities (cases 1, 2 and 4) and the childbearing history of cerebral palsy child (case 3). No overlapping phenotypes were observed in cases 1, 2 and 4, which might indicate phenotypic diversities in prenatal phenotypes for 16p11.2 microdeletion. All four fetuses showed normal karyotypic results while CMA identified 0.303–0.916 Mb microdeletions of 16p11.2, encompassing BP2–BP3 and BP4–BP5 regions separately. According to the parental CMA verification, case 1 carried a maternal inherited duplication in the region of Xp22.33 and a de novo deletion in the region of Xp21.1. All parents opted for the termination of pregnancies based upon genetic counselling.ConclusionOur findings enriched the intrauterine phenotypic features of 16p11.2 microdeletions, which would be beneficial for genetic counselling in clinic. In addition, preimplantation genetic testing was recognized as a first-tier approach for such carriers if they intended to conceive again.     

Chromosomal study after radioactive synoviorthesis for haemophilic haemarthrosis

Summary Twenty joints in 19 haemophiliacs were treated by radioactive synoviorthesis with gold (Au 198) to prevent recurrent haemarthrosis. Twelve knees, six elbows and two ankles were treated in two separate groups (29. 9. 76 and 9. 5. 77).In eight cases (40%) no further haemarthrosis occurred. A diminution of bleeding was obtained in nine cases (45%), a total of 85% good results with 15% failures. One failure in the first group (an elbow) had a second synoviorthesis and was included in the second group also.Prior to synoviorthesis the joint was scanned with technetium (Tc99m) to compare the inflammation of the synovium with that of six months later. The technique including the dosage of Tc99m, Au 198, and factor VIII cover is presented.A leucocyte culture was performed in 16 cases to study any chromosomal breakage, by banding and fluorescent techniques.Paper read at the SICOT meeting in Kyoto, Japan, October 1978     

Absence of ATM truncations in patients with severe acute radiation reactions

Purpose: Severe acute toxicity limits the effective use of radiotherapy in patients who are radiosensitive, and it is not usually possible to identify these radiohypersensitive (R-H) individuals before treatment commences. Five such R-H patients were detected over a 3-year period. We undertook this study to determine whether the severe acute radiohypersensitivity of these five individuals showed any correlation with cellular and molecular parameters known to be abnormal in radiosensitivity-related syndromes such as ataxia–telangiectasia (A-T).

Methods and Materials: Lymphoblastoid cells were isolated from fresh blood from the 5 R-H individuals who had previously demonstrated clinical R-H at least 9 months prior to sampling. Lymphoblastoid cell lines (LCLs) were established to determine the extent of postradiation chromosomal aberrations, cell cycle delay, cell proliferation, and tumor suppressor p53 protein stabilization. The polymerase chain reaction (PCR) and protein truncation (PTT) assays were used to test for the possibility of mutations in the gene mutated in A-T, termed ATM.

Results: LCLs derived from R-H subjects retained a significantly higher degree of radiation-induced chromosomal aberrations when compared to normal control LCLs. p53 stabilization by ionizing radiation appeared normal in all but one R-H subject. There was no evidence of A-T gene truncation mutations in any of the R-H subjects tested.

Conclusions: All R-H subjects in this study had their cellular radiosensitivity confirmed by the chromosomal aberration assay. Delayed p53 stabilization at 4 hours postirradiation in one R-H subject suggested that different etiologies may apply in the radiohypersensitivity investigated in this study.     

DNA修复基因XRCC1多态性与辐射损伤易感性的关系

目的研究DNA修复基因XRCCl多态性与辐射损伤易感性的关系。方法采用1：1配对病例对照设计,在对唐山市放射人员体检的基础上,以113名出现染色体畸变的射线工作人员为病例组,按性别、年龄(±5岁)、民族、工种配对,选择与病例在同一工作岗位、工龄相等或稍长(≤2年)、累积受照剂量相同或相近且无辐射损伤的放射人员为对照组(113名)。以多聚酶链反应-限制性长度多态性分析技术(PCR-RFLP)检测XRCCl基因,比较不同基因型与辐射损伤易感性的关系。结果病例组XRCCl 26304TT变异基因型频率为18．58%,高于对照组(7．08%),差异有统计学意义(P＜0．05)；携带此种基因型个体发生辐射损伤的风险比携带其他基因型者高3．47倍(OR=3．47,95% CI 1．43～8．44)。XRCCl G27466A和G28152A基因型频率在两组中的分布差异无统计学意义(P＞0．05)。结论XRCCl C26304T基因多态性与辐射致染色体畸变有关联。未发现XRCCl G27466A和G28152A基因多态性与辐射致染色体畸变有关。     

守宫木细胞与遗传毒性实验研究

目的：以体外试验研究野生蔬菜守宫木的细胞毒性和遗传毒性。方法：生（Ⅰ）和煮熟（Ⅱ）的守宫木匀浆液分别以40000、20000、10000、5000、2500、1250μg／ml浓度对CHL细胞染毒，每一浓度分别在24、48和72h时间点以中性红摄入方法对守宫木的细胞毒性进行评定；体外染色体畸变试验则以同样的浓度分别以生和煮熟的守宫木匀浆液染毒2h后，收获细胞制备中期相，对染色体结构畸变进行分析。结果：中性红摄入细胞毒性试验：在生的与煮熟的守宫木匀浆液细胞毒性剂量效应关系分析中，低剂量组随着染毒浓度加大细胞毒性增强，而在较高剂量组则出现随染毒浓度加大细胞毒性减弱，20000和40000μg／ml剂量组出现细胞的增殖现象；时间效应分析中有和剂量效应分析相似的现象，即在低剂量组随着染毒时间的延长细胞毒性增强，而从10000μg/ml剂量组开始随着染度时间的延长细胞毒性减弱并出现细胞的增殖现象；对生的与煮熟的守宫木细胞毒性进行比较分析，仅在染毒24h的20000μg／ml剂量组发现煮熟的守宫木匀浆液的细胞毒性有统计学意义（P〈0．05）地高于生的守宫木匀浆液。体外染色体畸变试验结果阴性。结论：守宫木在一定浓度范围内对细胞溶酶体和高尔基体有一定的损伤作用，未观察到守宫木对细胞的遗传物质染色体有损害作用，未发现不同的食用习惯对守宫木的毒性有影响。