口服长效避孕药甲基炔诺酮妇女的淋巴细胞姐妹染色单体互换的研究

口服长效避孕药甲基炔诺酮妇女的淋巴细胞姐妹染色单体互换的研究张卫红，易淑君，童月英，司宝敏，丁明，陶永琏（云南省计划生育技术科学研究所，昆明云南省第一人民医院妇产科６５００００）普遍认为姐妹染色单体互换（简称ＳＣＥ）可作为揭示化学诱变和致癌原对染色体...     

肝癌患者的细胞遗传学研究

对30例诊断为原发性肝癌(简称肝癌,下同)患者的细胞遗传学研究结果提示,染色体数。目畸变主要表现为四倍体和核内复制增多,分别为1.30％和3.07％;染色体结构畸变的各种类型均出现,畸变率为2.60％,其中尤以染色单体断裂和三射体、四射体的检出最为显著;G带核型分析未见异常;SCE(姐妹染色单体互换)率为10.12±2.44/细胞、0.22±0.05/染色体;MN(微核)率为2.80‰。以上各项异常检出率均高于对照组(P<0.01),有非常显著意义。     

6种常用抗癌药物对体外培养淋巴细胞遗传损伤的研究

背景与目的： 探讨几种常用抗癌药物的遗传毒性和潜在致癌性。 材料与方法： 选取异环磷酰胺、阿霉素、长春花碱、三尖杉酯碱、白消安和光神霉素6种常用抗肿瘤药物,分别在不同药物浓度作用下对健康人外周血进行短期微量全血培养。制作淋巴细胞染色体标本和姐妹染色单体互换(sister chromatid exchange, SCE)标本,分析核型,计算染色体畸变率和姐妹染色单体互换率,以此判断抗癌药物遗传毒性和潜在致癌性。 结果： 在6种实验药物中,异环磷酰胺、阿霉素、长春花碱、三尖杉酯碱各浓度组SCE频率和染色体畸变率均明显高于对照组(P<0.05);白消安高浓度组与对照组比较差异有统计学意义(P<0.05);而光神霉素与对照组间的差异无统计学意义(P>0.05)。结论： 异环磷酰胺、阿霉素、长春花碱、三尖杉酯碱和白消安均存在遗传毒性和潜在致癌性,光神霉素未发现类似毒作用。提示,职业性接触抗癌药物人员应建立起自我防护意识。     

鼻咽癌患者染色体断裂点脆性部位与姐妹染色单体互换关系的研究

 本文通过对鼻咽癌患者染色体断裂点、脆性部位与姐妹染色单体互换关系的研究，认为鼻咽癌患者染色体畸变断裂点、脆性部位和SCE无论在发生频率，累及染色体组别，还是在发生部位上都有一定相关。基于它们都反映染色体脆性的良好指标，因此在人群中尤其在某些肿瘤高发区，癌高发家族中进行检测，可能有助于确定肿瘤的起因和易感性，对早期发现癌患者有一定参考价值。     

染色体不稳定性与肿瘤发生的临床研究

关于肿瘤的发病机理，目前虽然还不太清楚，但是环境因素和遗传因素对肿瘤发生的影响已被许多研究证实。染色体的不稳定性是肿瘤发生的重要原因之一[1]。本文通过对肿瘤患者外周血淋巴细胞染色体畸变率和姐妹染色单体互换（SCE）率的研究，对染色体不稳定性和肿瘤发生的关系及肿瘤发生的遗传机理进行探讨。对象与方法一、对象：实验组：临床诊断为肿瘤30例，年龄在40－60岁之间。男18例，女12例。患者在术前取外周血，未接受放疗和化疗。对照组：正常人30例，其中男15例，女15例。年龄35－50岁。无诱变剂接触史。二、方法：①染色体畸变率…     

脱氧雪腐镰刀菌稀酮(DON)对中国仓鼠肺纤维CHL细胞的遗传毒性

脱氧雪腐镰刀菌释醇(DON)是能引起人畜中毒的赤霉病麦中含有的一种重要毒素。迄今DON的致突变性尚不明确。本文采用未曾报道的中国仓鼠肺纤维CHL细胞观察DON的致染色体畸变作用和姐妹染色单体互换率(SCE)的影响等细胞遗传毒性。     

体外培养人淋巴细胞动力学和姐妹染色单体互换的研究

本文以BudR-Giemsa技术检测研究了390名正常人外周血淋巴细胞动力学参数和姐妹染色单体互换(SCE)频率。结果表明:年龄与细胞动力学参数和SCE频率密切相关,男女性别间有显著差异。我们发现M_1、M_2为正偏态分布,M_3和增殖率指数(PRI)为负偏态分布。由于M_2的正偏态分布导致了SCE的正偏态分布;而3M_3的权重大于1M_1、2M_2,加剧了PRI的负偏态形成。SCE频率与M_1、M_2和M_3的分配相关。M_1、M_2与SCE频率呈正相关,M_3、PRI与SCE频率呈负相关。     

平阳霉素诱发人精子染色体结构畸变类型

人精子经平阳霉素处理后与去透明带地鼠卵受精，继而制备染色体进行核型分析．结果显示断裂是诱发畸变的主要类型，其后依次为互换、缺失、环和粉碎化；染色体型畸变的比例和均数远高于染色单体型；断裂型畸变的比例和均数远高于重接型．畸变中１７．３％为重接型，表明金黄地鼠卵母细胞中的ＤＮＡ损伤修复系统能够修复化学诱变所致人精子ＤＮＡ损伤．染色体型互换多于染色单体型互换提示：对这类损伤的修复，复制前修复系统可能比复制后修复系统作用更强．研究结果还证实染色体畸变精子和正常精子同样具有与卵受精的能力，提示人精子若反复或是期暴露于环境诱变因子，所产生的ＤＮＡ损伤有可能在精子中积累并在受精时不受选择性淘汰而传递给下一代．     

胃癌患者的染色体畸变分析

背景与目的:研究胃癌患者的染色体畸变情况.材料与方法:以临床已确定的未经放疗和化疗的26例胃癌患者作为研究组,以健康、无不良嗜好、无有害物接触史的志愿者26人作为对照组.采取研究组和对照组中每一例的外周血样本,各培养3个培养物,分别用于进行微核率、姐妹染色单体交换率、染色体结构和数目畸变率等指标的研究.结果:研究组均高于对照组,显示出研究组和对照组的微核率、染色单体交换率、染色体畸变率均存在着差异性.结论:染色体畸变可能是胃癌发生的细胞学基础.     

亚硫酸氢钠（二氧化硫）对人血淋巴细胞染色体畸变、姊妹染色单体互换及微核的效应

本文研究结果表明：亚硫酸氢钠(二氧化硫)，0．1mol／L浓度加入体外培养液，能够引起人血淋巴细胞姊妹染色单体互换(SCE)和微核(MN)率的增加，可使淋巴细胞有丝分裂周期延迟及细胞分裂指数下降．且这些作用有显著的剂量效应关系．亚硫酸氢钠在低浓度仅引起细胞染色单体畸变，在高浓度既可引起染色单体畸变，又可引起染色体型畸变。     

Characterization of chromosome aberrations induced by incubation at a restrictive temperature in the mouse temperature-sensitive mutant tsFT20 strain containing heat-labile DNA polymerase alpha

tsFT20 cells derived from a mouse mammary carcinoma cell line, FM3A, which has temperature-sensitive DNA polymerase alpha activity (Y. Murakami, H. Yasuda, H. Miyazawa, F. Hanaoka, and M. Yamada, Proc. Natl. Acad. Sci. USA, 82:1761-1765, 1985) were rapidly committed to death after temperature upshift to 39 degrees C. tsFT20 cells synchronized in S phase were more sensitive to the restrictive temperature than exponentially growing cells. In order to gain insight into the processes from the interruption of DNA synthesis to cell death, we analyzed chromosome aberrations induced in tsFT20 cells which had been incubated for 2 or 4 h at the restrictive temperature and then cultured at the permissive temperature. The majority of metaphase cells showed extensive chromosome aberrations such as chromatid gaps, breaks, and exchanges; chromosome pulverizations; their mixed types; and ring chromosomes. Analyses with the use of cell synchronization and autoradiography revealed that chromosome aberrations were induced only in the cells which synthesized DNA during incubation at 39 degrees C. We classified the chromosome aberrations into five types: gap or break type; exchange type; pulverization type; complex type; and ring type. The temporal order of the appearance of these types of chromosome aberrations was found to be the above described order. It was further found that cycloheximide dramatically repressed the induction of chromosome aberrations, and metaphases with many chromosome aberrations exhibited a large number of sister chromatid exchanges. These results indicate that abnormal cessation of DNA replication in tsFT20 cells at the restrictive temperature due to the inactivation of DNA polymerase alpha results in cell death via induction of double-strand breaks which lead to chromosome aberrations as well as sister chromatid exchanges.     

温石棉的遗传毒性及三种化合物的阻断作用

为了寻求一种理想的石棉表面改性剂,本研究观察了柠檬酸铝、混合稀土或亚硒酸钠对温石棉诱导人胚肺（ＨＥＬ）细胞染色体改变的影响。结果显示,温石棉可致ＨＥＬ细胞染色体畸变率和姊妹染色单体交换率升高。经三种化合物预处理的温石权,其所诱导的ＨＥＬ细胞的染色体畸变率和姊妹染色单体交换率均低于未处理温石棉组。提示,用三种化合物预处理温石棉,均可降低温石棉对细胞染色体的损伤作用,从而有可能减轻温石棉对人类的致癌     

The relationship between sister chromatid exchange, chromosome aberration and gene mutation induction by several reactive polycyclic hydrocarbon metabolites in cultured mammalian cells

The ability of three ultimate matabolites of benzo(a)-pyrene and of 7-bromomethylbenz(a)anthracene to induce 8-azaguanine mutants, sister-chromatid exchanges and chromosome aberrations has been investigated. 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene was shown to be an extremely efficient inducer of both mutants and sister-chromatid exchanges at 100% survival, whereas its geometrical isomer, 7 beta,8 alpha-dihydroxy-9 beta,10 beta-epoxy-7,8,9,10-tetrahydro-benzo(a)pyrene and benzo(a)pyrene-4,5-oxide were comparatively weak. The potency of this compound, as both a mutagen and a sister-chromatid exchange inducer, gives further evidence that it may be the important carcinogenic metabolite of benzo(a)pyrene. 7-Bromomethylbenz(a)anthracene was a moderate mutagen and inducer of sister chromatid exchanges. Comparisons of the relative potencies of these four chemicals as inducers of both mutations and sister chromatid exchanges have indicated that these two phenomena are not directly related. The induction of sister chromatid exchanges also appears to be independent of the induction of chromosome aberrations.     

Vulnerability of specific rat chromosomes to in vitro chemically induced damage.

The treatment of rat embryo secondary cultures with DMBA or DMBA-3H for 5, 9, or 24 h resulted in chromosome damage consisting mainly of chromatid type aberrations. There was an increase in the percentage of labelled nuclei and metaphases with increasing length of exposure. In terms of incidence of chromatid lesions, the largest telocentric chromosome (No. 2) was the most susceptible of the autosomes. Banding pattern analysis demonstrated that the region associated with negative band 2q24 of the No. 2 chromosome had the highest number of lesions. An increased accumulation of DMBA-3H label occurred in approximately the same chromatid area of a small fraction of cells exposed for either 5 or 9 h prior to mitosis. The complete loss of DMBA-3H chromosomal labelling after DNAse treatment suggests that the visible grains represent carcinogen-bound DNA. After DMBA and BrdUrd, there was an increase in the number of sister chromatid exchanges compared to controls treated with BrdUrd only; the location of the exchange points on chromosome No. 2 was similar in samples treated with either DMBA and BrdUrd or BrdUrd alone. Additional experiments with thymidine-3H showed that the non-random chromatid lesions on chromosome No. 2 may result from endogenous radiation from the incorporated tritium. These studies demonstrate that a specific chromosome may be affected by diverse agents and that chromatid lesions frequently occur at the site of sister chromatid exchanges.     

Cytogenetic effects of etoposide (VP-16) on human lymphocytes; with special reference to the relation between sister chromatid exchange and chromatid breakage

The effects of etoposide (VP-16) on sister chromatid exchange (SCE) and chromosome abnormalities were studied by using human peripheral lymphocytes. This drug produced a significant increase in the SCE frequency and chromosomal aberrations such as breaks, exchanges, and tetraploidy with or without endoreduplication. Analysis of the breakpoints of chromatid deletion with respect to their association with SCE in the metaphases from the second division demonstrated that VP-16-induced deletions arose with little dependence on the site of SCE. It is suggested that chromatid deletions induced by this drug derive from unrepaired chromatid breaks rather than from incomplete exchanges.     

Chromosomal alterations in peripheral blood lymphocytes, urinary mutagenicity and excretion of polycyclic aromatic hydrocarbons in six psoriatic patients undergoing coal tar therapy

Six male non-smoking subjects treated for psoriasis with topical applications of pure coal tar or 4% coal tar-containing ointment were examined in order to assess the genotoxic risk associated with this type of therapy. Mutagenicity in urine samples collected before and during the coal tar therapy was evaluated in the plate incorporation assay on Salmonella typhimurium strain TA98 in the presence of S9 mix and beta-glucuronidase. Total urinary polycyclic aromatic hydrocarbon (PAH) levels were evaluated in parallel by high resolution gas chromatography/mass spectrometry. In addition, sister chromatid exchanges and chromosomal aberrations were also analysed in peripheral blood lymphocytes collected before, during and after the end of the coal tar applications. The results suggest that urinary mutagenicity levels as well as the frequencies of chromosome aberrations and sister chromatid exchanges in lymphocytes are related to the levels of exposure to coal tar. Moreover the kinetics of repair of chromosome damage in relation to different exposure levels and the capacity of the urinary mutagenicity assay to correctly identify the exposure to significant levels of PAH are discussed.     

Cytogenetic studies on the in-vitro genotoxicity of 4-nitroquinoline-1-oxide on human-lymphocytes

Using the UV-mimetic mutagen 4-nitroquinoline-1-oxide (4NQO) to induce genetic damage in human cells (lymphoblastoid lines and primary cultures of peripheral blood samples), chromosome aberrations were induced by treating the cells with 4NQO at 1 X 10(-5) M for 24 h. The overwhelming majority of chromosome aberrations was of the chromatid (S + G2) type instead of the chromosome (G1) type. The most common chromatid aberrations were simple breaks, isochromatid breaks, and chromatid exchanges. When the number of chromatid breaks per cell value was used as a measurement for 4NQO sensitivity, lymphoblastoid cells from a xeroderma pigmentosum patient showed the highest sensitivity, followed by the cells of two melanoma patients and normal persons. These preliminary results suggest that 4NQO may be employed to develop an assay system as a biomarker for determining UV sensitivity in the human population.     

Increased incidence of chromosomal aberrations in peripheral lymphocytes of retired nickel workers

Chromosomal aberrations and sister chromatid exchanges wereanalysed in the peripheral lymphocytes of nine retired nickelrefinery workers 4 – 15 years after the retirement andcompared with 11 matched non-nickel exposed controls. None ofthe controls had previous occupations with known relation toinduction of chromosomal aberrations nor sister chromatid exchanges.The groups were equal as to socio-economic status and environmentalfactors other than the occupational ones, which could influencethe chromosome parameters, were to the largest possible extentexcluded. The nickel workers' previous occupational employmentinvolved exposure to inhalation of furnace dust of Ni₃S₂ andNiO or aerosols of NiCl₂ and NiSO₄. The concentration of nickelin the working atmospheres has been higher than 1.0 mg/m³ airand the exposure time more than 25 years. The retired nickelworkers showed an increased incidence of breaks (p <0.001)and gaps (p <0.05) but no difference in the incidence ofsister chromatid exchanges when compared with the controls.     

汉防己甲素对小鼠遗传毒性的研究

通过精子畸形试验,微核试验及姐妹染色单体变换试验,进行了汉防己甲素对小鼠遗传毒性的实验研究,结果表明：汉离己甲素组的小鼠精子畸形率及小鼠骨髓细胞微核率显著增高,且与微核率之间存在剂量－反应关系。但小鼠姊妹染色单体交换频率的改变不显著,表明该药对实验动物具有遗传毒性。     

Sodium fluoride-induced morphological and neoplastic transformation, chromosome aberrations, sister chromatid exchanges, and unscheduled DNA synthesis in cultured syrian hamster embryo cells

The effects of exposure of early-passage Syrian hamster embryo cells in culture to sodium fluoride have been studied with respect to induction of morphological and neoplastic transformation, chromosome aberrations, sister chromatid exchanges, and unscheduled DNA synthesis. Exposure of Syrian hamster embryo cells to NaF concentrations between 75 and 125 micrograms/ml for 24 hr caused approximately 90 to 40% cell survival and resulted in a dose-dependent increase in the frequency of morphological transformation of the cells. Mass cultures of cells treated with NaF (75 or 100 micrograms/ml) for 24 hr, followed by continuous cultivation for 35 to 50 passages, developed the ability to grow in soft agar and to produce anaplastic fibrosarcomas when injected into newborn hamsters. In contrast, no morphological and neoplastic transformation was observed in untreated cells. Furthermore, a significant increase in chromosome aberrations at the chromatid level, sister chromatid exchanges, and unscheduled DNA synthesis was induced by NaF in a dose- and time-dependent manner. These results indicate that NaF is genotoxic and capable of inducing neoplastic transformation of Syrian hamster embryo cells in culture. A potential for carcinogenicity of this chemical, which is widely used by humans, is suggested. However, the carcinogenic risk of this chemical to humans may be reduced by factors regulating in vivo dose levels.