三种毒物对小鼠受精卵染色体畸变的影响

本文采用小鼠受精卵染色体分析方法，对敌枯双、重铬酸钾、二硫化碳三种毒物的生殖细胞遗传物质诱变作用进行了评价，结果证明阴性对照组染色体数目畸变细胞率为９．Ｏ％，与各染毒组比较均有显著差异，敌枯双组为５１．８％，（Ｐ＜０．０１）；重铬酸钾组为３３．８％，（Ｐ＜０．０１）；二硫化碳（１０ｍｇ／ｍ３）组为２２．８％，（Ｐ＜０．０１），（１００ｍｇ／ｍ３）组为２｝８％，（Ｐ＜０．０１）。     

^60Coγ射线全身照射与离体照射诱发人精子染色体畸变研究

本文采用人精子染色体制备技术，分析了两名６０Ｃｏ事故性全身受照者照后６，７年的精子染色体畸变和用摸拟两受照者睾丸剂量离体照射后的健康人精子染色畸变。结果显示：在相同剂量点，离体照射组染色体畸变率显著高于全身受照组（Ｐ＜００１）；两受照组均以断裂型畸变为主，但全身受照组重接型畸变的比例显著增高；全身受照组Ｙ－精子与Ｘ－精子的比例显著增高（１６０∶１）。提示：生殖细胞在不同的发育阶段的遗传危害与对射线的敏感性是两个不同的概念，精子染色体重接型畸变的检测对评价电离辐射效应具有一定意义。两受照组Ｙ－精子与Ｘ－精子之比的差异提示辐射引进Ｘ连锁显性致死性突变的可能性。     

高剂量硒诱发姐妹染色单体交换及染色体畸变

为阐明正常人体外周血淋巴细胞培养物中加硒的遗传毒性剂量及其毒性特征,用不同剂量的亚硒酸钠处理培养中的淋巴细胞７２ｈ,观察其姐妹染色单体交换（ＳＣＥ） 及染色体畸变率的变化。结果显示在培养体系中添加０．０５ － ０ ．２５ｍｇ／Ｌ剂量的亚硒酸钠不增加ＳＣＥ 频率（ Ｐ＞０ ．５ － ０．２） 和染色体畸变率（ Ｐ＞ ０－５） ,添加０．７５ － １ ．５０ ｍｇ／ Ｌ 剂量的亚硒酸钠显著增加ＳＣＥ频率（ Ｐ＜ ０．０１） 及染色体畸变率（Ｐ＜ ０ ．０１ －０ ．００１） ,表现出遗传毒性。较高剂量的亚硒酸钠（０．７５ － １ ．５０ ｍｇ／Ｌ） 还可导致染色体形态不良和着丝粒早裂。     

CD3AK对晚期肝癌疗效初步观察

目的观察晚期肝细胞癌（ＨＣＣ）患者采用抗ＣＤ３抗体激活的杀伤细胞（ＣＤ３ＡＫ）治疗的效果。方法５８例晚期ＨＣＣ患者分为三组，Ａ组［ＣＤ３ＡＫ＋肝动脉化学栓塞（ＴＡＣＥ）］２２例，Ｂ组（ＣＤ３ＡＫ）１５例，Ｃ组（ＴＡＣＥ）２１例。结果部分缓解率（ＰＲ）Ａ，Ｂ，Ｃ组分别为４５．５％、１３．３％（Ｐ＜０．０５）和１４．３％（Ｐ＜０．０５），中位生存期分别为１１．３月、４．９月（Ｐ＜０．０１）和４．１月（Ｐ＜０．０１），半年和１年生存率分别依次为６８．２％，３３．３％（Ｐ＜０．０５）和２３．８％以及４０．９％、６．６％（Ｐ＜０．０５）和９．５％（Ｐ＜０．０５）。结论本组结果表明ＣＤ３ＡＫ＋ＴＡＣＥ治疗晚期ＨＣＣ疗效最佳     

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％     

鼻咽癌患者染色体端粒联合与染色体畸变关系的研究

为了探讨鼻咽癌染色体端粒联合与染色体畸变的关系，采用Ｇ显带技术，对２５例鼻咽癌患者外周血的染色体端粒联合频率进行观察，同时与染色体畸变的关系进行了分析。结果表明：鼻咽癌患者染色体端粒联合频率（３５．０７％）及染色体畸变率（１２．３３％）均显著高于对照组（２０．２７％及２．４６％），２者有非常显著性差异（Ｐ＜０．０１）。端粒联合的位点与染色体畸变断裂点在染色体上的分布密切相关（γ＝０．８１４９，Ｐ＜０．０５），说明染色体端粒联合发生是染色体畸变形成的机理之一。     

重铬酸钾对人精子染色体畸变率的影响

本文介绍了人精子经重铬酸钾体外染毒后，与去透明带金黄地鼠卵受精、体外培养制备人精子染色体进行核型分析。结果表明各染毒组（１０Ｙｍｇ／Ｌ、２０ｍｇ／Ｌ、４０ｍｇ／Ｌ）染色体断裂均数分别为０．１３２０、０．２５００、０．３６７６，与阴性对照组比较，中、高剂量组均具有显著差异（Ｐ＜０．０１、Ｐ＜０．０１）．而且具有剂量效应关系。     

^60Coγ射线离体照射诱发人精子和淋巴细胞染色体畸变的比较

本文对＾６０Ｃｏγ射线离体照射诱发的人精子和淋巴细胞染色体畸变进行了分析。在对照，１．０１，１．８１和２．９９Ｇｙ剂量组，两类细胞的畸变细胞率和结构畸变率基本相同。细胞畸变类型明显不同，精子染色体以断裂型畸变为主，是淋巴细胞断裂型畸变的４倍；淋巴细胞以互换型畸变为主，是精一换型畸变的７倍。讨论了两类细胞染色体畸变类型差异的可能原因及用电离辐射诱发淋细胞染色体畸变的结果外推其对策生殖作用的可行性。     

氯乙烯中毒性肝病和乙型肝炎染色体畸变分析

本文对２１例氯乙烯中毒性肝病、９例乙型肝炎患者及１０例正常人外周血淋巴细胞染色体Ｇ显带分析表明：中毒性肝病组、乙肝组染色体数目畸变率和结构畸变率均明显高于对照组（Ｐ＜０．０１）．其中氯乙烯中毒性肝病组染色体结构畸变率还高于乙肝组（Ｐ＜０．０１）。对结构畸变中断裂点的分析表明，两种肝病的断裂点分布不同，同时还发现染色体上某些位点断裂频率较高，并初步探讨了这些位点和肿瘤发生之间的关系。     

醋酸铅,氯化汞对小鼠精子染色体畸变及其受精卵发育的影响

分别用醋酸铅（１ｍｇ／ｋｇ·ｗｔ）和氯化汞（Ｏ．５ｍｇ／ｋｇ·ｗｔ）给雄性性成熟昆明种小鼠染毒，共染毒７０天，然后用染毒雄性小鼠与非染毒雌性小鼠交配，取受精卵观察卵发育状况并制备受精卵染色体。结果表明，醋酸铅染毒组（２６．８％）和氯化汞染毒组（３６．４％）受精卵发育异常率，均明显高于非染毒组（１３．３％）（Ｐ＜０．０１）。两组精子染色体数目异常率（１１．９８％和１０．８０％）也高于非染毒组（８．６３％）。但无统计学差异（Ｐ＜０．０５）。     

Increased chromosome-type chromosome aberration frequencies as biomarkers of cancer risk in a blackfoot endemic area

To examine whether biomarkers such as sister chromatid exchanges (SCEs) and chromosome aberrations (CAs) can predict cancer development, a nested case-control study was performed in a blackfoot endemic area with a known high cancer risk. A cohort of 686 residents was recruited from three villages in the blackfoot endemic area. Personal characteristics were collected, and venous blood was drawn for lymphocyte culture and stored in a refrigerator. The vital status and cancer development were followed using the National Death Registry, Cancer Registry, and Blackfoot Disease Registry. The follow-up period was from August 1991 to July 1995. During this 4-year period, 31 residents developed various types of cancer. Blood culture samples from nine of these subjects were unsuitable for experiments due to improper storage. Finally, a total of 22 cancer cases had cytogenetic samples that could be analyzed. Twenty-two control subjects were selected from those who did not develop cancer in the study period, and these subjects were matched to cases by sex, age, smoking habits, and residential area. The results showed that there was no significant difference in the frequencies of SCE and chromatid-type CAs between the case and control groups. However, the frequencies of chromosome-type CAs, e.g., chromosome-type gaps, chromosome-type breaks, chromosome-type breaks plus exchanges, total chromosome-type aberrations, and total frequencies of CAs in the case group, were significantly higher than those in the control group (P < 0.05). The odds ratio of cancer risk in subjects with more than zero chromosome-type breaks was 5.0 (95% confidence interval = 1.09-22.82) compared to those with zero chromosomal breaks. The odds ratios for more than zero chromosome-type breaks plus exchanges and a frequency of total chromosome-type aberrations of >1.007% were 11.0 and 12.0, respectively (P < 0.05). Subjects with a total CA frequency of >4.023% had a 9-fold increase for cancer risk. These results indicate that chromosome-type CAs are good biomarkers for the prediction of cancer development, whereas SCEs and chromatid-type CAs cannot predict cancer risk.     

不同种类诱导物致人类细胞染色体畸变效应

本文通过四类不同化学诱导物：５－氟尿嘧啶脱氧核苷ｆｌｕｏｒｏｄｅｏｘｙｕｒｉｄｉｎｅ（ＦＵＤＲ），ａｐｈｉｄｉｃｏｌｉｎ（ＡＰＤ），咖啡因ｃａｆｆｅｉｎｅ以及丝烈霉素Ｃｍｉｔｏｍｙｃｉｎｃ（ＭＭＣ）按照正交设计对正常人外周血进行染色体畸变诱导实验，通过染色体断裂、裂隙以及统计分析表明：四种化学诱导物单独作用于血标本时，均可极显著地诱导染色体畸变；不同组别染色体的畸变效应有别；不同种类诱导物之间有一     

The production of chromosomal alterations in human lymphocytes by drugs known to interfere with the activity of DNA topoisomerase II. I. m-AMSA

The frequencies of chromosomal aberrations and sister chromatid exchanges (SCE) were studied in human peripheral lymphocytes after exposure of whole blood cultures to the antitumour agent m-AMSA. Chromosome-type aberrations were found in cells exposed before stimulation or during the G1-phase of the cell cycle. Chromatid-type aberrations were obtained in cells exposed during the S- and G2-phases, but also in cells exposed the G1-phase or before stimulation. Treatment of lymphocytes with m-AMSA in the G1-phase or before stimulation had the additional effect of strongly increasing the frequency of SCE. When unstimulated lymphocytes were exposed to m-AMSA, the frequencies of SCE and chromatid-type aberrations, but not the frequency of chromosome-type aberrations, could be strongly reduced by holding the cells in F-10 for 2-4 h before stimulation, or by changing the growth medium after stimulation. A 1-h incubation in growth medium was sufficient for obtaining this reduction. The medium in which the m-AMSA-treated cells were incubated for the first 3 h after stimulation proved to be capable of inducing chromatid-type aberrations in late S/G2-phase and SCEs in the S-phase. These observations show that the chromatid-type aberrations and SCEs obtained by exposing unstimulated lymphocytes to m-AMSA were not produced during the treatment itself, but after stimulation at an advanced stage of the cell cycle by an active substance (m-AMSA or a metabolite of m-AMSA) released into the medium during the first hours of incubation. Post-treatments in G2 with 1-beta-D-arabinofuranosylcytosine (ara-C) and hydroxyurea strongly enhanced the frequency of chromatid-type aberrations obtained after treatment of stimulated or unstimulated lymphocytes with m-AMSA. Post-treatments in unstimulated or G1-phase lymphocytes with ara-C did not influence the frequency of chromosome-type aberrations induced by m-AMSA at these stages, but strongly enhanced those induced by X-rays.     

人精子诱变检测中新体外代谢活化系统的研究

人精子与去透明带金黄地鼠卵受精,在受粗后异合卵培养阶段,用终浓度分别为２０μｇ／ｍｌ、４０μｇ／ｍｌ、４０μｇ／ｍｌ、６０μｇ／ｍｌ的间接诱变剂环磷酰胺进行处理,继而制备精子染色体进行核型分析。得到环磷酰胺诱发的染色体畸变精子率在上述剂量组依次为３３％、５０％、３３％;断裂均数依次为０．５４、１．９４和０．７２。与空白对照组比较,差异具有显著性。本研究结果表明,用人精子／金黄地鼠异合卵为靶细胞,能     

Caffeine enhances radiosensitization to orthotopic transplant LM3 hepatocellular carcinoma in vivo

The aim of this study was to determine whether caffeine enhanced radiosensitization in an orthotopic transplant of LM3 human hepatocellular cancer in nude mice. LM3 hepatocellular carcinoma cells were infected with red fluorescent protein and irradiated, and cell cycle distribution and survival fraction were detected. A nude mouse model of orthotopic transplant of red fluorescent protein‐expressing LM3 hepatocellular cancer was established. Nude mice were divided into four groups: control (NS); caffeine (Caff) alone; irradiation (IR) alone; and caffeine + IR (Caff + IR). Tumor growth curves were described. Expression of cyclin and apoptosis were evaluated by analysis of phosphorylated cyclin dependent kinase 1 (CDC2) Tyr15 (CDC2‐Tyr15‐P), cyclinB1, TUNEL staining, and caspase‐3. Caffeine abrogated IR‐induced G₂ phase arrest and decreased survival of irradiated LM3 cells. Caffeine enhanced radiosensitivity of LM3 hepatocellular cancer in vivo. Tumor growth delay time in the Caff + IR group was 14.3 days compared with the NS group, 14.1 days compared with the Caff alone group, and 7.2 days compared with the IR alone group. At 15 Gy, expression of CDC2‐Tyr15‐P in the Caff + IR group (26.0 ± 8.9%) was significantly lower than in the IR alone group (68.4 ± 10.6%), expression of cyclinB1 and proportion of TUNEL‐positive cells in the Caff + IR group (30.4 ± 8.7% and 59.2 ± 9.5%, respectively) was significantly higher than in the IR alone group (7.0 ± 3.7% and 24.2 ± 7.2%, respectively), expression of caspase‐3 was consistent with the TUNEL staining results. This study suggested that caffeine might enhance the radiosensitivity of LM3 hepatocellular cancer in vivo, and may be feasible for further clinical applications. (Cancer Sci 2010)     

Chromosome aberrations induced by etoposide (VP-16) are not random

The clastogenic effect of etoposide, an anti-cancer chemotherapeutic drug, was investigated in vitro on lymphocytes of 5 healthy donors. The analysis of the first division metaphases arising after mutagenesis in G1 phase shows that chromosome-type aberrations are much more frequent than chromatid-type lesions. The distribution in relation to chromosome lengths of the 439 breakpoints that were accurately identified is not random: chromosomes 1, 11 and 17 are most frequently involved, while chromosomes 4, 5 and X are seldom affected. This non-random distribution may be related to chromosome structure, since R-band-rich chromosomes are significantly more affected than G-band-rich chromosomes.     

Adriamycin-induced chromosome aberrations in human fibroblasts.

Adriamycin (AM) induced chromosome lesions and cell division delay in human foreskin fibroblasts. Cells treated with 0.01, 0.03, and 0.05 mug AM/ml culture medium for 1 hour and evaluated 5-12 hours post treatment exhibited a wide spectrum of cytogenetic injuries, ranging from moderately damaged metaphases with predominantly simple chromatid-type lesions to heavily damaged metaphases with chromosome stickiness and fragmentation. In moderately damaged metaphases that could be scored for specific types of aberrations, we observed a paucity of chromatid exchanges and chromosome-type lesions even in cultures having a very high frequency of breakages. Further, the distribution of breaks among chromosomes within groups A-G appeared to be random, which suggested that the drug does not show breakage specificity in human fibroblasts; The number of heavily damaged metaphases increased with an increase in concentration of AM and with longer periods of recovery.     

A study of the effect of anti-tumor agents combined with caffeine on established lines of human osteosarcoma cells and primary cultured human sarcoma cells by clonogenic assay

A study on the effect of anti-tumor agents combined with caffeine on sarcoma cells was carried out by clonogenic assay. The materials used were an established line of human osteosarcoma cells (OST strain) and twelve surgically resected or biopsied specimens. Caffeine showed a marked synergistic effect on sarcoma cells with the DNA-damaging agents, ADR, CDDP, CPM and MMC in terms of colony inhibition. In particular, 0.2 micrograms/ml CDDP with 2 mM caffeine showed a considerable synergistic effect on human sarcoma cells. Among the 12 cases, more than 50% colony inhibition was observed in 7 cases which were treated with this combination of CDDP with caffeine. Furthermore, a combination of 0.02 micrograms/ml CDDP (1/100 of peak plasma concentration) with 2 mM caffeine also showed more than 50% colony inhibition. Therefore, we assumed that caffeine was able to reduce the necessary dose of anti-tumor agent in some way. We stress that caffeine seems to be a very useful synergistic drug for causing lethality in sarcoma cells in combination with various DNA-damaging agents which are not effective on sarcoma cells.     

伐昔洛韦预防多发性骨髓瘤并发带状疱疹的有效性及对患者血清IFN-γ、IL-6水平的影响

目的:探讨伐昔洛韦预防多发性骨髓瘤并发带状疱疹的疗效及对患者血清IFN-γ和IL-6水平的影响。方法:将100例我院收治的多发性骨髓瘤患者随机分为观察组及对照组。两组患者均接受PAD化疗方案,观察组患者在此基础上口服盐酸伐昔洛韦片。比较两组患者治疗后的疗效、带状疱疹发生率及不良反应发生情况;比较两组患者治疗前及治疗后血清IFN-γ、IL-6及T淋巴细胞亚群(CD3＋、CD4＋、CD8＋及CD4＋/CD8＋)水平。结果:两组患者总有效率相比较无统计学差异(P＞0.05);观察组患者带状疱疹发生率(2.0%)低于对照组患者(20.0%)(P＜0.01);观察组患者恶心呕吐及乏力发生率均高于对照组患者(P＜0.05);治疗后,观察组患者血清IFN-γ水平高于对照组患者(P＜0.01),IL-6水平低于对照组患者(P＜0.01);治疗后,观察组患者血液CD3＋、CD4＋及CD4＋/CD8＋水平均高于对照组患者(P＜0.01),CD8＋水平低于对照组患者(P＜0.01)。结论:伐昔洛韦能够有效预防多发性骨髓瘤患者化疗期间带状疱疹的发生,不影响化疗的疗效,同时安全性较高,并能够调节IFN-γ、IL-6及T淋巴细胞亚群的水平。     

苏木抑制诱变效应的初步研究

在丝裂霉素(MMC)诱导下,生长中细胞的姊妹染色单体互换频率显著增高,环磷酰胺(C.C.P)可诱发高微核率,已被普遍认同。本文以SCE及微核率为检测指标,观察活血化瘀药物:“苏木”抗MMC及C.C.P的诱导。发现苏木对MMC、C.C.P的诱导有一定的抑制作用,但其本身也能致使细胞SCE升高。