肺癌患者染色体稳定性及诱变剂敏感性的研究

目的 探讨细胞染色体不稳定性与肺癌的关系。方法 采用微量全血培养法对２４例经病理证实但未治疗的原发性肺癌患者、２０例非癌性患者和２０名健康志愿者外周血淋巴细胞（ＰＢＬ）进行自发和诱发的染色体畸变和微核检测。结果人肺癌患者ＰＢＬ自发及诱发染色体畸变率和微核率明显高于非癌性肺病患者和健康者;肺癌患者具有较高的染色体畸变率和微核率。肺癌患者染色体稳定性较差。结论 细胞染色体稳定性评价对肺癌的早期诊断、鉴     

吸烟口腔白斑患者粘膜脱落细胞和外周血淋巴细胞DNA损伤关系的研究

目的与方法：本文对５４例口腔白斑患者进行了口腔脱落粘膜细胞核和外周血淋巴细胞微核及染色体畸变率检测。结果：吸烟的口腔白斑患者口腔脱落粘膜细胞微核细胞率和外周血淋巴细胞微核细胞率及染色体畸变率均显著高于正常人。且口腔白斑病员区的脱落粘膜细胞微核细胞率的变化与口腔白斑变程度相关,正常区膜脱落细胞微核细胞率的高低与外周血淋巴细胞微核细胞率呈正相关。结论：结果表明,口腔白斑病损区脱落粘膜细胞微核细胞率可反     

乳腺肿瘤患者外周血淋巴细胞的姐妹染色单体交换和染色体畸变

本实验观察了20例乳腺癌患者、19例乳腺纤维腺瘤患者及17例正常人的外周血淋巴细胞的姐妹染色单体交换(SCE)率及染色体畸变率,结果发现乳腺癌组的SCE率及染色体畸变率均比乳腺纤维腺瘤组和正常对照组显著增高(P<0.01),而后两组之间则无统计学差异(P>0.05)。经丝裂霉素C(MMC)诱导后的染色体畸变率在三组间也存在这种区别。作者认为:乳腺癌患者具有对癌肿的遗传易感性;观察淋巴细胞的SCE率及杂色体畸变率对于乳腺肿块的鉴别诊断以及乳腺癌的预防具有临床应用价值。     

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。     

膀胱癌患者染色体畸变及SCE的研究

作者对19例膀胱癌患者和16例正常人外周血淋巴细胞染色体畸变和SCE进行了研究。结果表明膀胱癌患者染色体总畸变率、断裂及裂隙、脆性位点的表达、四倍体、着丝粒后期相以及SCE率都明显高于正常人。对以脆性位点表达率和SCE率为指标检测群体中,尤其是高危群体中肿瘤易患性个体的可能性进行了讨论。     

针灸抗突变效应的实验研究

背景与目的： 以小鼠骨髓嗜多染红细胞微核率及染色体畸变率的变化,研究针灸的抗突变作用。材料与方法：以小鼠为实验动物,以环磷酰胺为诱变剂,分正常对照组,阳性对照组,针灸预防Ⅰ、Ⅱ组,针灸治疗Ⅰ、Ⅱ组,针刺实验组小鼠足三里、艾灸关元穴,检测小鼠骨髓嗜多染红细胞微核率及染色体畸变率的变化。结果： 阳性对照组与正常对照组比较骨髓嗜多染红细胞微核率及染色体畸变率升高,预防各组和治疗各组低于阳性对照组。 结论： 针灸可以拮抗由环磷酰胺诱导的小鼠骨髓嗜多染红细胞微核率及染色体畸变率的升高,具有抗突变作用。     

83. 三氯乙烯药疹样皮炎患者的染色体检查

目的：自1988年以来,中国广东先后在三氯乙烯（Trichloroethylene）接触工人中发现以皮损（严重的药疹样皮炎）、发热、肝功能损害和浅淋巴结肿大为主要表现的病例过100例,死亡20例,且近几年每年都约有30例左右发病。因其发病特殊,后果严重,诊断不易,发病机制尚未完全清楚,病因尚未完全确定,现有防治措施效果不太理想,故进行了系列研究。这是患者染色体水平的初步研究结果。方法：染色体核型分析（G带）和脆性分析按中山医科大学遗传教研室的方法,染色体畸变分析和微核分析按广东省职业病防治院毒理研究室方法进行。对三氯乙烯药疹样皮炎患者12例（其中男性7例;皮炎分型为剥脱性皮炎7例,重症多形红斑2例,大疱性表皮坏死松解症1例和多形红斑2例）进行染色体核型、畸变分析及微核分析;对6例剥脱性皮炎进行染色体脆性分析。结果：染色体核型分析：男性7例均为46,XY,女性5例为46,XX,未发现明显异常,染色体畸变分析（％）：总畸变率为0.917（范围1～3）;染色体型畸变率为0.25（0～2）;染色单体型畸变率为0.75（0～2）;微核细胞率为1.23‰±0.42‰（范围0～3）,均在本实验室正常范围内;外周血淋巴细胞染色体脆性分析也均未见明显异常。结论：三氯乙烯药疹样皮炎患者外周血淋巴细胞染色体的核型、畸变、脆性分析和微核分析均未发现明显异常。在上述的检测条件下,未发现三氯乙烯药疹样皮炎患者有任何染色体水平的改变。     

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.     

小剂量受照人员远期外周血淋巴细胞染色体畸变分析

本文对２６例小剂量（０．１０－０．３３Ｇｙ）受照人员受照２６－３１年后外周血淋巴细胞染色畸变和微核进行了分析。结果表明，受照组染色体畸变率和微核率都明显高于对照组，但染色体畸变率和微核率与受照剂量的相关关系已不存在；外照组染色体畸变率高略高于内照组，但在内照组中检出双着丝粒体和稳定性畸变，外照组中未检出。提示；不能排除在内照组人员体内仍有裂变产物内污染的存在。     

河南"4.26"60Co源辐射事故受照者细胞遗传学随访观察

背景与目的:对河南"4.26"60Co源辐射事故受照者进行细胞遗传学随访观察.材料与方法:利用微量全血培养法制备外周血淋巴细胞染色体和胞质分裂阻断(CB)微核标本,对河南新乡60Co源辐射事故6例受照者照后1～2年的染色体畸变和CB微核进行分析.结果:受照1～2年后受照者的染色体畸变率已明显下降,受照1年后非稳定性染色体畸变仍占有较大比例(40%～60%);受照2年后稳定性染色体畸变高于非稳定性染色体畸变,但差异无统计学意义(P＞0.05,1例受照者除外,其P＜0.01);受照1～2年后染色体总畸变率与受照剂量间仍有明显的剂量效应关系(r＜0.936,P均＜0.01);而受照1～2年后多数受照者的CB微核率已降到正常参考值范围.结论:随着照后时间推移,非稳定性染色体畸变逐渐丢失,稳定性染色体畸变仍保持在较高水平;微核分析不适用于大剂量受照个体远后遗传效应的评价.     

Sister chromatid exchanges (SCE), chromosomal aberrations and micronuclei of cultured peripheral lymphocytes in patients with lung cancer, miners and non-mining workers of the tin mine in Yunnan

Determination of SCE frequency, chromosomal aberration and micronucleus rate of cultured peripheral lymphocytes in 32 patients with lung cancer, 33 miners and 40 non-mining workers in Yunnan Tin Mine was carried out. The results showed that the cancer patients had higher SCE incidence, chromosomal aberration and micronucleus rate, the non-mining workers had the least and miners on an intermediate level. There was a significant difference of SCE, chromosomal aberrations and micronucleus rate between patients and non-mining workers (P less than 0.05-0.01). We also found that miners had a significant higher SCE and chromosomal aberration rate but not micronucleus rate as compared with the non-mining workers. We proposed that some carcinogens present in the Yunnan Tin Mine be responsible for the genetic damages in the miners. Chemical drugs may be considered to contribute to the genetic damage in cancer patients who had a tendency toward an increased SCE, chromosomal aberration and micronucleus rate as compared to the miners, though without reaching a statistical significance. We suggested that combination assay of SCE with chromosomal aberration or micronucleus be an useful index for screening of the high risk population and monitoring the chemical drug prevention of lung cancers in Yunnan Tin Mine.     

小细胞肺癌患者外周血淋巴细胞染色体不稳定性分析

采用低叶酸、高ｐＨ的微量全血细胞培养法，观察２０例小细胞肺癌患者和２０例正常人的外周血淋巴细胞染色体不稳定性，发现实验组染色体畸变率及异常细胞率明显高于对照组（Ｐ＜０．０１），结果表明小细胞肺癌患者存在体细胞染色体不稳定性，人群中部分个体染色体不稳定性增加和癌症的易感性增加有关。     

Sister chromatid exchange induction by benzo(a)pryene in cultured peripheral blood lymphocytes of lung cancer patients and healthy individuals with or without familial history of neoplasms

The inducibility of sister chromatid exchanges (SCEs) by benzo(a)pyrene (BP) was studied in cultured peripheral blood lymphocytes of 15 untreated lung cancer patients and 25 healthy persons including 11 high- and 14 low-cancer-risk individuals tentatively classified by the familial history of lung cancer and other neoplasms. The baseline SCE frequency in cultured lymphocytes was significantly high in lung cancer patients, as compared with all healthy persons or low-cancer-risk individuals. Following exposure to BP, the lymphocytes of lung-cancer patients and high-cancer-risk individuals exhibited significantly greater SCE yields than those of persons at low risk, although no significant difference was observed in the lymphocyte SCE yields when the levels of lung cancer patients were compared with those of all healthy persons. A comparison of the net SCE increase (delta SCE) in BP-exposed lymphocytes among the study groups, however, revealed a significant difference in delta SCE values only between high- and low-cancer-risk individuals. The present findings on both the observed SCE yields and delta SCE values suggest that lymphocytes of high-risk individuals may be more susceptible to BP-induced DNA damage than those of persons at low risk, and that such a chromosomal hypersensitivity to genotoxins may be associated with a high risk of neoplasms.     

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。     

Serial Measurement of Sister Chromatid Exchanges in the Peripheral Lymphocytes of Patients with Lung Cancer Receiving Chemotherapy in Relation to Bone Marrow Toxicity

The frequencies of sister chromatid exchanges (SCE) in the peripheral lymphocytes of patients with lung cancer before and after initial chemotherapy were serially measured and the correlation between SCE frequencies and bone marrow toxicity was evaluated. The addition of mitomycin C to vindesine plus cisplatin increased SCE frequencies significantly in patients with non-small cell lung cancer. A significant increase in frequencies of SCE was observed in patients treated with cyclophosphamide plus adriamycin plus vincristine as compared with those treated with cisplatin plus etoposide in small cell lung cancer. A significant inverse correlation was observed between SCE frequencies in the peripheral lymphocytes 7 days after treatment ( x ) and the nadir value/pretreatment value of platelets ( y )( r = -0.685, P = 0.0007, y = 0.842–0.022 x ). The relation between SCE frequency and leukopenia showed the same trend as thrombocytopenia, but the correlation was not statistically significant ( r = - 0.444, P = 0.057). SCE assay may have potential clinical use for the prediction of chemotherapyinduced thrombocytopenia.     

Serial measurement of sister chromatid exchanges in the peripheral lymphocytes of patients with lung cancer receiving chemotherapy in relation to bone marrow toxicity

The frequencies of sister chromatid exchanges (SCE) in the peripheral lymphocytes of patients with lung cancer before and after initial chemotherapy were serially measured and the correlation between SCE frequencies and bone marrow toxicity was evaluated. The addition of mitomycin C to vindesine plus cisplatin increased SCE frequencies significantly in patients with non-small cell lung cancer. A significant increase in frequencies of SCE was observed in patients treated with cyclophosphamide plus adriamycin plus vincristine as compared with those treated with cisplatin plus etoposide in small cell lung cancer. A significant inverse correlation was observed between SCE frequencies in the peripheral lymphocytes 7 days after treatment (x) and the nadir value/pretreatment value of platelets (y)(r = -0.685, P = 0.0007, y = 0.842-0.022x). The relation between SCE frequency and leukopenia showed the same trend as thrombocytopenia, but the correlation was not statistically significant (r = -0.444, P = 0.057). SCE assay may have potential clinical use for the prediction of chemotherapy-induced thrombocytopenia.     

四物汤抗环磷酰胺诱变作用的研究

目的： 研究四物汤抗环磷酰胺的诱变作用。方法：小鼠骨髓细胞实验中,设四物汤高、中、低剂量组[分别为9.36、4.68、2.34 mg/(kg·d)],环磷酰胺(cyclophosphamide,CP)阳性对照组和空白对照组,四物汤各组以不同浓度药液给小鼠连续灌胃7 d,阳性对照组和空白对照组灌服等量生理盐水。于第7天灌胃后,四物汤各组和阳性对照组小鼠腹腔注射CP 20 mg/kg,24 h后处死动物,取股骨骨髓细胞制备微核标本和染色体标本。人外周血淋巴细胞实验中,四物汤设高、中、低剂量[分别为3.36、1.68、0.84 g/(kg·d)],以家兔含药血清的形式加入淋巴细胞培养液中,四物汤各组和阳性对照组均在培养液中加入10-5 mg/mL 的CP,空白对照组加入等量生理盐水。培养72 h后收获细胞,制备微核标本和染色体标本。在光镜下观察、计数含微核及染色体畸变的细胞数,计算微核率及染色体畸变率。结果：四物汤3个剂量组在上述测试系统中,与阳性对照组比较,微核率及染色体畸变率均明显降低,差异有统计学意义 (P＜0.01);与空白对照组比较,微核率及染色体畸变率差异均无统计学意义 (P＞0.05)。结论：在本实验条件下,四物汤有明显的抗环磷酰胺诱变的作用。     

鼻咽癌患者染色体断裂热点与SCE高发位点、脆性部位、原癌基因位点的相关研究

采用在染色体标本上同时显示ＳＣＥ及Ｇ带带型的方法，对鼻咽癌患者染色体断裂热点与ＳＣＥ高发位点、染色体脆性部位及原癌基因位点之间的相关性进行了分析。结果表明：患者的ＳＣＥ频率、染色体畸变率均显著的高于对照组（Ｐ＜０．０１），患者的染色体断裂点和ＳＣＥ位点都主要分布在染色体的Ａ、Ｂ、Ｃ、Ｄ组和浅带上，且两者所累及的染色体号存在着明显的相关（ｒ＝０．９５７６，Ｐ＜０．０１），患者的１５个断裂热点与ＳＣＥ高发位点的一致率为５３．３３％，与脆性部位的一致率为８０％，与原癌基因位点的一致率为４０％