肺癌患者染色体不稳定性与遗传易感性关系的研究

检测了30例肺癌患者阿糖胞苷诱导的外周血淋巴细胞染色体的不稳定性。结果表明患者组自发、诱发的畸变细胞率和染色体畸变率均显著高于对照组。说明肺癌患者染色体不稳定性高是其患癌易感性的重要遗传基础。作者认为以自发性染色体畸变率5％为标准对在人群中筛选肿瘤易患个体将有积极意义。     

医院放射人员染色体畸变与累积辐射剂量的关系研究

目的 探讨医院放射人员染色体畸变与累积辐射剂量的关系.方法 选取唐山市各级医院放射人员1217例,行染色体检查和累积辐射剂量监测,根据工种、工龄、医院级别进行分组.选取具有可比性的非放射人员170例为对照组,行染色体检查.分析染色体畸变与累积辐射剂量的关系.结果 工种间比较,依对照组、放射诊断组、介入治疗组、放射治疗组、核医学组顺序,染色体畸变率(dic畸变率、ace畸变率、染色单体型畸变率、合计)呈增长趋势;依放射诊断组、介入治疗组、放射治疗组、核医学组顺序,累积辐射剂量呈增长趋势(P<0 c.05).工龄间比较,依对照组、≤10年1、0<~≤20年、20<~≤30年、30<年顺序,染色体畸变率(dic畸变率、ace畸变率、染色单体型畸变率、合计)呈增长趋势;依≤10年1、0<~≤20年、20<~≤30年、30<年顺序,累积辐射剂量呈增长趋势(P<0.05).医院级别间比较,依对照组、二甲以下、三甲、二甲顺序,染色体畸变率(dic畸变率、ace畸变率、染色单体型畸变率、合计)呈增长趋势;依二甲以下、三甲、二甲顺序,累积辐射剂量呈增长趋势(P<0.05).染色体畸变与累积辐射剂量呈明显正相关性.结论 工龄越长,累积辐射剂量越大,染色体畸变率越高.医院放射人员应该注重防护工作.     

不良孕产史夫妇的细胞遗传学分析

本研究课题针对我院遗传咨询门诊的妇科患者进行细胞遗传学检查，从1060例患者中检出30例染色体异常患者，异常率2.8%，女性多于男性。异常类型主要为易位(15例)、例位(11例)，且发现随着习惯性流产的发生时间越晚，染色体畸变率越低。     

乳腺癌患者体细胞染色体畸变的初步观察

本文用稳定性核型分析方法,对30例乳腺癌患者的淋巴细胞进行染色体畸变分析。结果患者的染色体畸变明显高于正常对照组,多畸变细胞明显增高,还出现了额外大断片、额外小染色体、巨大染色体等。其对肿瘤的诊断、预后可能有一定的参考价值。     

染色体畸变核型分析

目的明确染色体畸变核型特点,为人类遗传性疾病的诊治提供参考依据。方法取受检者外周血,进行淋巴细胞培养,常规制备染色体,G显带,镜下计数50个中期分裂相,显微摄影分析10个核型。结果在1065例生殖咨询者中,染色体畸变率为15.7%。其中按畸变类型分类,数目畸变率为9.9%,结构畸变率为2.3%,染色体多态性畸变率为3.5%;按染色体不同分类,常染色体畸变率为11.7%,性染色体畸变率为4.0%。结论人类常染色体易发生畸变,数目畸变是人类染色体畸变的主要类型,结构畸变多发生在常染色体中,染色体多态性以大Y和小Y为主。     

44例脑肿瘤病人外周血培养细胞染色体畸变及微核的检测

对２３例正常人和４４例脑肿瘤患者外周血培养细胞染色体畸变及微核进行检测发现：①脑肿瘤染色体数目畸变率和染色体结构畸变率均较正常人明显增高（Ｐ＜０．０１），在良性与恶性脑肿瘤组之间比较差异无显著性意义（Ｐ＞０．０５）；②微核率高低的顺序为恶性脑肿瘤组＞良性肿瘤组＞正常对照组，三者之间比较差异有显著性意义（Ｐ＜０．００１）。实验结果为脑肿瘤患者存在体细胞染色体不稳定性提供了实验依据     

鼻咽癌患者外周血细胞染色体畸变分析

用核型分析法对30例鼻咽癌患者外周血淋巴细胞染色体进行稳定性畸变分析。结果表明鼻咽癌患者染色体数目结构异常明显高于对照组,还出现了额外染色体和异常染色体克隆细胞。证明鼻咽癌患者体细胞存在一定程度的染色体不稳定性和细胞遗传学特征。     

胃癌患者外周血淋巴细胞微核,姊妹染色单体互换及染色体畸变的观察

对16例胃癌患者和16例正常健康人的外周血淋巴细胞的微核、姊妹染色单体互换(SCE)以及染色体畸变进行了观察和比较。结果发现,正常健康人和患者的微核率分别为0.053％和0.197％;SCE频率均值为6.34±0.46和10.17±1.24;染色体畸变率分别为2.71％和6.67％。胃癌患者均高于正常健康人,且有显著性差异。表明胃癌的发生与染色体不稳定性及DNA修复能力有关。     

父亲重度吸烟对胎儿绒毛细胞染色体畸变率的影响

对10例父母无吸烟习惯,10例父亲重度吸烟的胚胎绒毛细胞染色体畸变率进行研究,结果表明。父亲重度吸烟组染色体数目畸变率和结构畸变率同非吸烟组相比显著提高(P<0.05和P<0.01)。     

放射工作人员淋巴细胞微核率与染色体畸变关系分析

目的 分析放射工作人员淋巴细胞微核率与染色体畸变的关系。为放射工作人员体检观察射线损伤和受照剂量关系选择适当的检测指标。方法 选择淋巴细胞微核率异常升高的放射工作人员进一步做染色体畸变分析，微核检测和染色体畸变分析均采用培养法。结果 淋巴细胞微核率异常升高者中，染色体畸变阳性率为16.32%,男性高于女性；染色体畸变阳性率和染色体畸变率均有随着微核率升高而升高的趋势。结论 在射线损伤效应中，微核率异常先天染色体畸变异常；随着微核率升高，出现染色体畸变的可能性也随之增加。因此，放射工作人员体检应先检查淋巴细胞微核，微核率显著升高者再进一步做染色体畸变分析。     

Cytogenetic analysis using fluorescence in situ hybridization (FISH) to evaluate occupational exposure to carcinogens

Chromosomal aberrations determined by conventional method or fluorescence in situ hybridization (FISH) technique with whole chromosome painting are used as biomarkers of effect. Groups occupationally exposed to 1,3-butadiene (BD), acrylonitrile, ethyl benzene and benzene in petrochemical industry, and carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) from ambient air were followed by conventional method and FISH painting for chromosomes # 1 and # 4, in total 383 subjects, including controls. No effect was observed by either method with exposure to 1,3-butadiene < 1mg/m(3) and acrylonitrile < 0.3mg/m(3). Ethyl benzene and benzene exposure significantly increased chromosomal aberrations by both methods, which decreased after the implementation of preventive measures. The genomic frequency of translocations by FISH calculated as FG/100 was significantly increased in city policemen versus control group exposed to c-PAHs from ambient air (1.72+/-1.57 versus 1.25+/-1.11, P<0.05). The method of FISH with whole chromosome painting seems to be more sensitive to detect chromosomal injury by occupational exposure to carcinogens than conventional method.     

Lack of sensitivity of sister-chromatid exchange for lymphocyte chromosomal damage detection caused by antichagasic treatment

No studies exist on sister-chromatid exchange (SCE) formation in chagasic patients therapeutically exposed to nifurtimox (NFX) or benznidazol (BZ). In the present study SCE was analyzed in cultures of peripheral lymphocytes of patients aged 11 months to 11 years treated with NFX 12-15 mg/kg/d for 60 days or with BZ 5 mg/kg/d for 30 days. Chagasic patients before treatment constituted a control group. A mean of 30 metaphases were examined for each individual. All treated patients compared with untreated controls did not show a significant increase in SCE frequency. Compared with the percentage of chromosomal aberrations in these patients and others belonging to the same epidemic protocol, SCE seems to be less sensitive in the detection of lymphocyte chromosomal damage caused by NFX or BZ.     

Prevention of chromosomal aberration in mouse bone marrow by indole-3-carbinol.

In this study, we report the protective effect of indole-3-carbinol (I3C), one of the glucobrassicin derivative isolated from cruciferous vegetables against cyclophosphamide induced chromosomal aberrations in mouse bone marrow cells. The three test doses namely 1000,500 and 250 mg/kg b.wt. of I3C provided protection when given 48 h prior to the single i.p. administration of cyclophosphamide (50 mg/kg). I3C alone did not induce chromosomal aberrations at the test doses of 1000 and 500 mg/kg b.wt.. Thus tested glucobrassicin derivative seems to have a preventive potential against cyclophosphamide induced chromosomal aberrations in Swiss mouse bone marrow cells at the doses tested.     

Genotoxic effects of chlorophenoxy herbicide diclofop-methyl in mice in vivo and in human lymphocytes in vitro

Diclofop-methyl (DM) is a chlorophenoxy derivative used in large quantities for the control of annual grasses in grain and vegetable crops. In this study, the genotoxic effects of DM were investigated by measuring chromosomal aberrations (CAs) in mouse bone-marrow cells and CA and the comet assay in human peripheral lymphocytes. Mice were treated with 15.63, 31.25, 62.5, and 125?mg/kg body weight of DM intraperitoneally for 24 hours, and 15.63-, 31.25-, 62.5-, 125-, and 250-μg/mL concentrations were applied to human lymphocytes for both 24 and 48 hours. In in vivo treatments, DM significantly, but not dose dependently, increased the total chromosome aberrations, compared to both negative and solvent controls. Cell proliferation was significantly, but not dose dependently, affected by all doses. In in vitro treatments, DM (except 15.63 μg/mL) significantly and dose dependently increased the frequency of chromosome aberrations. Also, 250 μg/mL of 48-hour treatment was found to be toxic. Cell proliferation was significantly and dose dependently affected by DM applications, when compared to negative control. In in vitro treatments, DM significantly decreased the mitotic index only at the highest concentration for 24 hours, and 62.5- and 125-μg/mL concentrations for 48 hours. In the comet assay, a significant and dose-dependent increase in comet-tail intensity was observed at 62.5-, 125-, and 250-μg/mL concentrations. The mean comet-tail length was significantly increased in all concentrations. Our results demonstrate that DM is genotoxic in mammalian cells in vivo and in vitro.     

Chromosomal aberrations in human lymphocytes exposed in vitro to enrofloxacin and ciprofloxacin

Chromosomal aberrations were evaluated in cultures of human peripheral lymphocytes from eight healthy donors, exposed to the antimicrobial enrofloxacin (EFX) or to its major metabolite ciprofloxacin (CFX). In both treatments cultures revealed an increase in the chromosomal aberration level, detected as chromatid and chromosome breaks and gaps. Control cultures analysis revealed 3.6 +/- 0.6 chromosomal aberrations per 100 cells while treated cultures exhibited 8.3 +/- 0.8 and 9.6 +/- 1.2 aberrations at 5 and 50 microg/ml of EFX respectively. In CFX treated cultures it was found 5.6 +/- 1.3 and 7.7 +/- 3.5 aberrations/100 cells at 5 and 25 microg/ml antimicrobial concentration. These results suggested a genotoxic effect of EFX and CFX in the system used (P < 0.001). A reduction in the mitotic index and fuzzy metaphases were observed at 50 microg/ml of CFX, indicating a cytotoxic effect produced by this antimicrobial.     

Genetic toxicity of taxol

研究了抗肿瘤新药紫杉醇的致突变性及致癌潜能，结果表明，紫杉醇在１～５０００μｇ／皿范围内，无论有无Ｓ９活化系统对沙门氏菌株四株（ＴＡ９７，ＴＡ９８，ＴＡ１００，ＴＡ１０２）标准测试菌株均无致突变性．但在小鼠骨髓细胞微核试验和ＣＨＬ细胞染色体畸变分析试验中，均显示了阳性反应．紫杉醇在２０，４０，８０ｍｇ·ｋｇ－１诱导的小鼠骨髓多染红细胞微核率分别为１９．３‰，２９．３‰，４７．１‰，均明显高于阴性对照的２．２‰（Ｐ＜０．０１）。染色体畸变分析表明，非活化条件下在２０～１６０μｇ·Ｌ－１范围内，活化条件下在８０～６４０μｇ·Ｌ－１范围内，紫杉醇可使ＣＨＬ细胞染色体畸变增加．畸变类型主要为染色体数目改变，表明其作用点是纺缍体而不是ＤＮＡ．本研究结果显示了紫杉醇的致癌潜能，也为其临床应用的风险效益评价提供了有价值的资料．关键词紫杉醇；沙门氏菌；微核；染色体畸变     

Mutagenicity tests of the antithyroid agent thiamazole. Cytogenetic studies on male mice

The mutagenic potential of thiamazole, an antithyroid agent, was investigated by an in vivo cytogenetic test and was compared with those of mitomycin C and vincristine. These drugs were subcutaneously injected into slc-ICR male mice either as a single dose or as multiple doses for 5 successive days. Thiamazole (90 or 180 mg/kg) did not increase the number of micronuclei in bone marrow cells. This drug also did not induce chromosomal aberrations in spermatogonium, spermatocyte, or bone marrow cells. On the other hand, mitomycin C (3.0 mg/kg) increased the appearance of chromosomal aberrations and micronuclei. Vincristine (0.2 mg/kg) induced bone marrow cells with a so called large micronucleus (d greater than or equal to D/4). These results suggest that thiamazole may not have significant effects on the genetic systems of mice.     

Genotoxic effects of chlorophenoxy herbicide diclofop-methyl in mice in vivo and in human lymphocytes in vitro

Diclofop-methyl (DM) is a chlorophenoxy derivative used in large quantities for the control of annual grasses in grain and vegetable crops. In this study, the genotoxic effects of DM were investigated by measuring chromosomal aberrations (CAs) in mouse bone-marrow cells and CA and the comet assay in human peripheral lymphocytes. Mice were treated with 15.63, 31.25, 62.5, and 125?mg/kg body weight of DM intraperitoneally for 24 hours, and 15.63-, 31.25-, 62.5-, 125-, and 250-µg/mL concentrations were applied to human lymphocytes for both 24 and 48 hours. In in vivo treatments, DM significantly, but not dose dependently, increased the total chromosome aberrations, compared to both negative and solvent controls. Cell proliferation was significantly, but not dose dependently, affected by all doses. In in vitro treatments, DM (except 15.63 µg/mL) significantly and dose dependently increased the frequency of chromosome aberrations. Also, 250 µg/mL of 48-hour treatment was found to be toxic. Cell proliferation was significantly and dose dependently affected by DM applications, when compared to negative control. In in vitro treatments, DM significantly decreased the mitotic index only at the highest concentration for 24 hours, and 62.5- and 125-µg/mL concentrations for 48 hours. In the comet assay, a significant and dose-dependent increase in comet-tail intensity was observed at 62.5-, 125-, and 250-µg/mL concentrations. The mean comet-tail length was significantly increased in all concentrations. Our results demonstrate that DM is genotoxic in mammalian cells in vivo and in vitro.     

Chromosomal aberrations in workers exposed to low levels of benzene: association with genetic polymorphisms

Benzene and its metabolites damage human lymphocytes, resulting in chromosomal aberrations and aneuploidy. Polymorphisms in the genes for benzene-metabolizing enzymes have been implicated in benzene-associated haematotoxicity. In this study, we examined the specificity of benzene-induced aneuploidy and the influence of genetic polymorphisms (GSTM1, GSTT1, GSTP1, NAT2, NQO1 and CYP2E1) on chromosomal aberrations. In total, 82 benzene-exposed workers from a coke oven plant and 76 matched controls were examined. The benzene concentration in the work-place air ranged from 0.014-0.743 p.p.m. (geometric mean 0.557 p.p.m.). Benzene exposure was associated with significant increases in both monosomy and trisomy of chromosomes 8 and 21. Translocations between chromosomes 8 and 21 [t(8:21)] were eight-fold more frequent in the high-level exposure group compared to the control group. Multiple regression analysis indicated that the frequencies of chromosome aberrations were significantly associated with benzene exposure and polymorphisms in the metabolic enzyme genes. A particular subset of genotypes, which included the GSTM1-null and GSTT1-null genotypes, the slow acetylator type of NAT2, a variant of the NQO1 genotype and the CYP2E1 DraI and RsaI genotypes, were either separately, or in combination, associated with increased frequencies of aneuploidy among the benzene-exposed individuals after adjustments for age, alcohol consumption and smoking. These results suggest that polymorphisms in the genes for benzene-metabolizing enzymes influence the susceptibility of individuals to chromosomal aberrations in relation to benzene exposure.     

Cytogenetic effects of quinalphos in mice

The cytogenetic effect of quinalphos was studied in Swiss albino mice using the micronucleus test, bone marrow and germ cell chromosome assays and sperm morphology assay. Quinalphos at 5, 10 and 15 mg/kg body weight was administered orally to mice. Quinalphos induced micronuclei in the bone-marrow cells of mice and also caused a significant increase in chromosomal aberrations in bone-marrow cells (at 10 and 15 mg/kg body weight dose levels) and in germ cells (at all tested doses). A high incidence of abnormal sperms was also observed in mice treated with quinalphos.