苯中毒、石棉肺和有害气体中毒患者体细胞及生殖细胞的遗传损伤

目的对苯中毒、石棉肺、有害气体中毒者体细胞及生殖细胞的遗传损伤程度进行比较，为职业病防护与生殖健康研究提供依据。方法用常规法检测174名职业病患者（包括48例苯中毒、71例石棉肺、55例有害气体中毒）及80名健康人员的外周血淋巴细胞染色体畸变率和微核发生率，并取男性精液行精子畸形率与突变检测。结果3组患者染色体畸变率、微核发生率和精子畸形率依次为：苯中毒患者0．4％、1．52‰、（62±14）％；石棉肺患者0．51％、2.31‰、（41±7）％；有害气体中毒患者0．42％、1．55‰、（48±8）％，均明显高于对照组[0．20％、0．34‰、（27±5）％]，差异有统计学意义（P〈0．05）。石棉肺组的染色体畸变率和微核发生率高于其他组，但无统计学意义（P〉0．05）；苯中毒组的精子畸形率高于其他组，差异具有统计学意义（P〈0．05）。此外，在苯中毒患者精子中检测到了遗传物质的新突变。结论苯中毒、石棉肺、有害气体中毒者不仅存在体细胞遗传物质的损伤，还可能发生生殖细胞的遗传突变。     

Comparison of micronuclei induction for X-ray and ultrasound exposures of Vicia faba root meristem cells

X-irradiation (200R) but not ultrasound (1.1 MHz, 8 W/cm² peak, 1 min continuous exposure) induced micronuclei formation in root meristem cells of Vicia faba 6–36 hr post-exposure.     

Inhibition of nucleotide excision repair (NER) by microcystin-LR in CHO-K1 cells

Microcystin-LR (MC-LR), a potent inhibitor of PP1 and PP2A protein phosphatases, is related to tumor promotion and initiation. Although the genotoxic properties of this toxin have been extensively investigated with a variety of non-mammalian and mammalian test systems, the existing results are contradictory. Based on our previous results regarding the impact of MC-LR on the processes of DNA repair we decided to examine in greater detail its effect on the capacity of nucleotide excision repair (NER). CHO-K1 cells were pre-treated with increasing doses of MC-LR (1, 10 and 20 μg/ml) and then exposed to UV radiation (25 J/m²). Apoptosis was analyzed to exclude the possibility of false positive results in the comet assay. The results suggest that MC-LR targets the nucleotide excision repair mechanisms by interference with the incision/excision phase as well as the rejoining phase of NER and leads to an increased level of UV-induced cytogenetic DNA damage in CHO-K1 cells.     

染色体不稳定性及HPV、CMV感染与宫颈癌发病的关系

目的 :探讨染色体数目畸变、脆性位点发生率、姐妹染色单体交换发生率、细胞内微核发生率、宫颈分泌物内人乳头状瘤病毒 (HPV)感染、巨细胞病毒 (CMV)感染与子宫颈癌的关系。方法 :对 30例子宫颈癌患者 ,做外周血细胞培养 ,分析染色体畸变、姐妹染色单体交换、脆点和微核。用PCR方法扩增宫颈分泌物HPV16 -DNA、HPV18-DNA、CMV -DNA。结果 :染色体畸变 ,姐妹染色单体交换发生率 ,脆性位点、细胞内微核发生率与正常对照组差异有显著性 ,宫颈癌组HPV16 -DNA、HPV18-DNA和CMV -DNA感染阳性率分别为 50 %、46 .67%和 53 .33 % ,3者均为阳性者占 2 0 %。结论 :染色体不稳定性增加及HPV、CMV感染与宫颈癌发病相关     

丙烯酰胺诱导NIH 3T3细胞微核染色体的双色荧光原位杂交分析

目的 分析丙烯酰胺（ＡＡ）诱导的ＮＩＨ３Ｔ３小鼠成纤维细胞微核（ＭＮ）染色体组成,判断其遗传毒性。方法 用着丝粒和端粒ＤＮＡ探针双色荧光原位杂交检测ＭＮ的染色体组成。结果 ＡＡ诱导的ＮＨ３Ｔ３小鼠成纤维细胞总ＭＮ率和既含着丝粒信号的ＭＮ率均有显著的剂量－反应关系（r＝０．９９２９、０．９９３,Ｐ＜０．０１）。高剂量（４ ００rg/ml）时,ＡＡ诱导的ＭＮ中６５．９％既含着丝粒信号又含端粒信号;２６．０％     

Evaluation of the in vivo genotoxicity of liposomal formulation for delivering anticancer estrogenic derivative (ESC8) in a mouse model

The genotoxic potential of glucocorticoid receptor (GR)-targeted liposomal formulations of the anticancer drug molecule ESC8 was studied in vivo. A methodical literature review discovered no previous studies on the genotoxicity of ESC8. Genotoxicity was assessed in both male and female mice by various assay systems, such as comet assay, chromosomal aberrations and micronuclei assay, which detect different abnormalities. Eleven groups of male mice and eleven groups of female mice, containing six animals per group, were used in the present study: group I served as vehicle control; group II received the positive control (cyclophosphamide 40 mg/kg; CYP); and animals in group III to XI received free drug (ESC8), DX liposome and drug-associated DX liposomal formulation (DXE), respectively, dissolved in 5% solution of glucose at a drug-dose of 1.83, 3.67 and 7.34 mg/kg, respectively. Same drug treatments were followed for the female mice groups. The obtained data revealed the safety of DXE, which did not show substantial genotoxic effects at different dose levels. In contrast, the positive control, CYP, exhibited highly substantial irregular cytogenetic variations in comparison with the control group in different assays.     

Abnormal Nuclear Structures (Micronuclei,Nuclear Blebs,Strings, and Pockets) in a Case of Anaplastic Giant Cell Carcinoma of the Thyroid: An Immunohistochemical and Ultrastructural Study

The authors report a case of a 70-year-old woman with an anaplastic giant cell thyroid carcinoma, along with immunohistochemical and electron microscopic findings. Histologically, the tumor is characterized by mononucleated and multinucleated giant cells, lack of architectural cohesion, atypical mitoses, and extensive areas of coagulative necrosis. Tumor cells showed AE1/AE3 positivity as well as nuclear overexpression of p53 and ki-67. Semithin sections revealed multiple nuclei with heterogeneous size ranging from micronuclei to large-size (giant) nuclei. Micronuclei were confirmed by electron microscopy that disclosed also the presence of nuclear blebs, strings, and pockets. Morphological findings of these abnormal nuclear structures in conjunction with p53 and Ki-67 nuclear overexpression suggested a faulty mitotic checkpoint/mitotic catastrophe in the progression of anaplastic giant cell thyroid carcinoma.     

生川乌提取物遗传毒性研究

[目的]选用目前新药遗传毒性评价中推荐使用的3种试验方法(小鼠骨髓微核试验、鼠伤寒沙门氏菌回复突变试验、体外CHL细胞染色体畸变试验)研究生川乌的遗传毒性.[方法]小鼠骨髓微核试验设3个生川鸟提取物给药剂量组(26.0、13.0、6.5 g生药/kg)、阴性对照组和阳性对照组(环磷酰胺40 mg/kg).Ames试验选用两种方法:直接法和代谢活化法.试验菌株为鼠伤寒沙门氏组氨酸缺陷型菌株TA97、TA98、TA100、TA102、TA1535,生川乌提取物在试验中设6个剂量组(5.000、2.500、11250、0.625、0.313、0.156 mg生药/皿),同时设自发回复突变对照组、阳性对照组.体外CHL细胞染色体畸变试验也选用两种方法:直接法和代谢活化法.试验设5个生川乌提取物浓度组(5.000、2.500、1.250、0.625、0.313 mg生药/ml),阴性对照及阳性对照组.[结果]小鼠骨髓微核试验生川乌提取物各剂量组小鼠骨髓多染红细胞微核率与阴性对照组相比,差异无统计学意义(P>0.05).Ames试验生川乌提取物在加或不加肝微粒体酶(S9)时均未见引起TA97、TA98、TA100、TA102、TA1535试验菌株基因突变,即Ames试验阴性,试验重复一次,所得结论相同.体外CHL细胞染色体畸变试验生川乌提取物在加或不加S9时均未引起CHL细胞的染色体畸变,试验结果为阴性,试验重复1次,所得结论相同.[结论]在本实验室条件下,生川乌提取物在小鼠骨髓微核试验、Ames试验及体外CHL细胞染色体畸变试验中均为阴性结果,故认为在本实验条件下,生川乌提取物无遗传毒性.     

底泥重金属铅对鲤鱼红细胞遗传物质的损伤

目的 研究河流底泥重金属污染对水生生物遗传物质的损伤。方法 在含不同浓度Pb^2 的底泥环境下饲养鲤鱼，取其红细胞涂片、染色，测定其微核细胞率。结果 底泥Pb^2 含量在196．23—2519．60mg/kg范围内时，随Pb^2 浓度升高，鲤鱼红细胞的微核细胞率也升高(P＜0．01)，表现出明显的量效关系。同时观察到，随高浓度的Pb^2 作用时间延长，红细胞的微核细胞率有升高的趋势。结论 河流底泥重金属铅污染对细胞遗传物质有损伤作用。     

Effect of a low-dose ethinylestradiol and gestodene in combination on the frequency of micronuclei in human peripheral blood lymphocytes of healthy women in vivo

BACKGROUND: Since most oral hormonal contraceptives contain a fixed combination of ethinylestradiol and gestodene as an estrogenic/progestogenic component, we decided to evaluate the possible mutagenic effect of a low-dose contraceptive pills containing 20 microg ethinylestradiol and 75 microg gestodene. METHODS: A total of 30 healthy women received hormonal contraception during six consecutive menstrual cycles. A single daily dose was 20 microg ethinylestradiol and 75 microg gestodene. The pills were taken orally in a monthly cycle of 3 weeks on and 1 week off. In the investigation of the mutagenic effect of these contraceptive pills in vivo, the cytokinesis block micronucleus (CBMN) test was used, and the frequency of micronuclei (MN) in peripheral blood lymphocytes was determined. RESULTS: Average MN frequency in women before therapy was 7.40 +/- 0.75 MN/1000 analyzed cells, and after therapy was 7.37 +/- 0.59 MN/1000 analyzed cells (p > 0.05). CONCLUSION: Our data suggest that oral contraception with 20 microg ethinylestradiol and 75 microg gestodene in combination during six consecutive menstrual cycles does not induce micronuclei in peripheral blood lymphocytes of women.