顺铂对小鼠骨髓遗传毒性的研究

给小鼠腹腔注射不同剂量（０．５,２．０,６．５和１３．０ｍｇ／ｋｇ）的顺铂,观察骨髓细胞有丝分裂指数、染色体结构畸变率及畸变细胞率的变化,以评价顺铂对小鼠在体骨髓细胞的遗传毒性效应。结果表明,０．５ｍｇ／ｋｇ剂量的顺铂即可使有丝分裂指数显著降低（Ｐ〈０．０５）,染色体结构畸变率和畸变细胞率显著增高（Ｐ〈０．００１,Ｐ〈０．０１）,几项检测指标均呈现较好的剂量反应关系。顺铂不仅可引起染色体损伤,而且     

d-筒箭毒碱对V79细胞和小鼠骨髓细胞有丝分裂的影响

目的：探讨烟碱型乙酰胆碱受体阻断剂ｄ－筒箭毒碱对Ｖ７９细胞和小鼠骨髓细胞有丝分裂的影响。方法：在离体情况下以受试物处理中国仓鼠Ｖ７９细胞，通过分析Ｖ７９细胞晚末期和早Ｇ１期细胞核与细胞质构型，双核细胞频率，探讨受试物对细胞质质裂的影响；研究同时探讨了活体情况下，该化合物对小鼠骨髓细胞的Ｃ－有丝分裂（Ｃ－Ｍ）效应，分析其对哺乳动物体细胞有丝分裂的影响。结果：ｄ－筒箭毒碱能使Ｖ７９细胞的晚末期一早Ｇ１     

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。     

桑椹对小鼠骨髓细胞诱发突变的抑制作用

本文用小鼠骨髓细胞微核试验方法和小鼠骨髓细胞染色体畸变试验方法观察了新鲜桑椹汁对环磷酰胺（ＣＰ）诱发小鼠骨髓嗜多染红细胞微核和染色体畸变的抑制作用。发现新鲜桑椹汁具有抑制环磷酰胺诱发骨髓微核率和染色体畸变率升高的作用，且有明显的剂量反应关系，相关系数分别为－０．９４和－０．９８。说明新鲜桑椹汁具有一定的抗诱变作用。     

维生素C对苯致小鼠骨髓细胞P53表达拮抗作用的研究

目的：探讨维生素Ｃ对苯致小鼠骨髓细胞Ｐ５３表达的影响。方法：采用静式吸入染毒的方法,共染毒３ｄ,并在其饮水中加入一定量的维生素Ｃ,用免疫组化方法测定小鼠在细胞Ｐ５３阳性率,并作Ｕ检验。结果：染毒３０ｄ后无一小鼠死亡,白细胞计数也在正常范围内,而ＰＣ５３表达则是最高浓度组高于对照组和其他染毒组（Ｐ〈０．０１或Ｐ〈０．０５）;维生素Ｃ摄入量每日每只小鼠在２．５ｍｇ以上可降低Ｐ５３表达阳性率;加入时间在染毒期２／３以上时也可降低Ｐ５３表达阳性率。结论：苯吸入对小鼠的骨髓细胞ＤＮＡ有一定的影响,维生素Ｃ具有一定的拮抗作用。     

绞股蓝多糖（GPS）生物学作用的研究

本文报道绞股蓝多糖（ＧＰＳ）的生物学作用－抗氧化作用、细胞免疫促进作用。实验结果表明：（１）ＧＰＳ５ｍｇ／只／天灌胃，能降低正常小鼠脂质过氧化（ＬＰＯ）水平（Ｐ〈０．０５），能提高正常小鼠超氧氧化物歧化酶（ＳＯＤ）活性（Ｐ〈０．０５）。（２）ＧＰＳ５０ｍｇ／只／天灌胃，能显著降低亚急性衰老模型小鼠脂质过氧化水平（Ｐ〈０．０１），能显著提高亚急性衰老模型小鼠超氧化物酶活性（Ｐ〈０．０１），（３）ＧＰ     

胎盘多肽对环磷酰胺抑制小鼠骨髓及白细胞作用的影响

目的：探讨ＰＰｓ对环磷酰胺ＬＬＰ诱导小鼠骨髓及周血白细胞作用的影响。方法：用ＣＰ诱导小鼠骨髓及周血白细胞抑制，并投以ＰＰｓ，观察骨髓细胞及周血白细胞的变化。结果ＰＰｓ对ＣＰ诱导的受试动物周血白细胞的降低与阳性对照组比较有明显升高作用（Ｐ〈０．０１），对ＣＰ诱导的动物骨髓抑制现象也有明显的保护作用（Ｐ〈０．０１），并且与阴性对照组比较，ＰＰｓ对正常小鼠血白细胞及骨髓细胞均无明显影响，结论：ＰＰｓ可望     

维生素E拮抗氯化汞致小鼠微核作用的研究

本文采用微核试验方法对维生素Ｅ（ＶｉｔＥ）拮抗氯化汞（ＨｇＣｌ２）致小鼠胸骨骨髓多染红细胞微核作用进行了研究，其主要结果有：（１）给小鼠ＶｉｔＥ５ｍｇ／ｋｇ体重及以上剂量时，可显著地降低ＨｇＣｌ２１．０ｍｇ／ｋｇ体重的致小鼠微核作用（Ｐ〈０．００１）；（２）在ＨｇＣｌ２（１．０ｍｇ／ｋｇ）给小鼠染毒前４ｈ和染毒后２ｈ内补充ＶｉｔＥ２０ｍｇ／ｋｇ体重时，均显示明显地拮抗微核作用（Ｐ〈０．００１～Ｐ〉     

聚乙二醇修饰重组人白细胞介素－2的体内抗小鼠宫颈癌作用

聚乙二醇（ＰＥＧ－８０００）化学修饰重组人白细胞介素－２（ＰＥＧ－ｒＩＬ－２）显著地延长了ｒＩＬ－２的循环半衰期。本研究比较了不同剂量方案的ＰＥＧ－ｒＩＬ－２和ｒＩＬ－２的体内抗小鼠宫颈癌作用，采用局部用药抗移植的小鼠腹水瘤型和皮下实体瘤型宫颈癌Ｕ１４。结果表明：腹腔内注射一定剂量的ＰＥＧ－ｒＩＬ－２（４５００ＩＵ，ＱＤ×５）能较相同剂量的ｒＩＬ－２显著延长荷腹水瘤小鼠的存活期（２３．１±３．６天比１６．５±２．０天，Ｐ＜０．０１），但ＰＥＧ－ｒＩＬ－２剂量过低则无明显疗效。在小鼠皮下移植肿瘤的局部并于肿瘤移植后的第４天开始注射给药，不同剂量的ＰＥＧ－ｒＩＬ－２（１５００～１３５００ＩＵ，ＱＤ×５）对皮下移植瘤的生长抑制作用显著强于相同剂量的ｒＩＬ－２（Ｐ＜０．０１），且抗肿瘤作用呈剂量依赖效应。本研究提示，ＰＥＧ－ｒＩＬ－２的抗小鼠宫颈癌作用优于ｒＩＬ－２，对人宫颈癌的局部免疫治疗具有潜在的临床价值。     

生长抑素SMS201—995对小鼠结肠癌肝转移瘤的实验研究

本研究观察生长抑素衍生素ＳＭＳ２０１－９９５对ＢＡＬＢ／ｃ小鼠结肠腺癌肝转移瘤细胞周期的影响，检测血清ＣＥＡ水平的变化，并观察小鼠生存期的改变。采用流式细胞术。与对照组相比，ＳＭＳ２０１－９９５治疗组的瘤细胞增殖指数和Ｓ期细胞百分比明显降低（Ｐ〈０．０１）而Ｇ０／Ｇ１期细胞百分比则明显增加（Ｐ〈０．０１）。治疗组血清ＣＥＡ水平较对照组显著降低（Ｐ〈０．０５），生存期明显延长。治疗组细胞增殖指数，Ｓ     

ANEUPLOIDY INDUCTION BY THE WATER EXTRACT OF TRIPTERYGIUM HYPOGLAUCUM(LEVEL) HUTCH IN MOUSE BONE MARROW CELLS

The aneuploldy inducing activity of a Chinese medicinal herb, Tripterygium hypoglaucum (level) Hutch (THH) were investigated by means of thhree cytogenetic end points, namely C-mitotic (CM) effects, micronucleus (MN) and parallel chromosome structural aberration (CA) analyses in vivo. The experiments were performed on mouse bone marrow cells. THH showed similar gentoxic effects to colchicine (COL) in CM, MN and CA analyses; positive CM effects were observed accompanied with increases of mitotic index and frequencies of C-mltotic cells as well as decreased frequencies of anaphase in all of the THH-treated groups. The compound showed a positive MN response in bone marrow polychromatic erythrocytes but was negative in CA analyses. The preliminary results suggested that THH is an aneuploldy inducer in mouse bone marrow cells under present experiment conditions.     

茯苓对AFB1致突变的抑制作用

本文以小鼠骨髓嗜多染红细胞微核和染色体畸变为指标，检测了中药茯苓对黄曲霉毒素Ｂ１致突变作用的影响，结果表明，茯苓煎剂对显著地抑制ＡＦＢ１的致突变作用（Ｐ〈０．０５）并呈量效关系。     

海藻多糖的抗突变性研究

目的与方法 :本文选用小鼠骨髓嗜多染红细胞微核试验和小鼠精子畸形试验 ,对海藻多糖的抗突变作用进行研究。 结果 :海藻多糖对环磷酰胺诱发的微核率和精子畸形率有着显著的抑制作用 (P <0 .0 1)。结论 :提示海藻多糖对由环磷酰胺引起的体细胞和生殖细胞的基因突变有着明显的拮抗作用。     

A PCR-based clonal analysis of radiation-induced loss of heterozygosity in haemopoietic stem cells.

CBA mouse strains have been used for many years as a model of radiation-induced acute myeloid leukaemia and the leukaemias in CBA and their F1 hybrids are characterised by a specific loss of heterozygosity involving one homologue of chromosome 2. Previous cytogenetic studies of transplanted irradiated bone marrow, or of bone marrow obtained from irradiated mice significantly before the appearance of leukaemia, have been interpreted as the chromosome 2 deletion being a high frequency, possibly initiating event. However, these studies had not specifically addressed the question of whether the characteristic deletion was induced at a high frequency in stem cells. Using a PCR-based technique, we have studied the induction of chromosome 2 LOH in the progeny of (CBA/H x C57BL/6)F1 stem cells after a potentially leukaemogenic radiation exposure. Whilst chromosome 2 LOH can be induced directly by irradiation and there is a preferential loss of the CBA allele, the frequency is no greater than LOH induced in other chromosomal regions studied. The data do not support radiation-induced deletion involving one homologue of chromosome 2 in long-term repopulating stem cells (<1 in 200) being as high a frequency event as might be inferred by previous cytogenetic studies of total bone marrow.     

E838联合γ射线对淋巴瘤荷瘤小鼠的协同抑瘤作用

 目的 本研究主要观察E838对小鼠移植性淋巴瘤的体内抑瘤效果及相关的生物学指标，探讨合用137Cs γ射线是否具有抑瘤增效作用。方法 取2～3mm3淋巴瘤瘤块接种于IRM 2小鼠腋部皮下，24h后将荷瘤小鼠随机分为对照组、单放组、E838低、中、高药物组及药物合用照射组、环磷酰胺组。药物组与药物合用照射组对应性腹腔注射相同剂量E838，每日1次，连续7天，环磷酰胺隔日1次×4。合用照射组于给药的第4天进行全身1Gy照射，每日1次，连续5天。观察各组小鼠骨髓有核细胞数和肿瘤抑制率。结果 E838 3个剂量对小鼠移植性淋巴细胞瘤的抑瘤率分别为(44.14±15.96)%、(70.74±11.17)%和(50.00±18.09)%，与对照组比较差异有统计学意义(P<0.001)，骨髓有核细胞数与对照组相比则明显提高。E838合用137Csγ射线能提高抑瘤效果，抑瘤率分别为(65.43±2.13)%、(77.13±6.38)%和(67.55±11.17)%，(P<0.001)，对肿瘤的杀伤作用高于单放组和单药治疗组。结论 E838对小鼠肿瘤细胞具有良好的抑制作用，E838合用γ射线具有协同抑瘤作用，在适当剂量范围内可以促进荷瘤小鼠放疗后骨髓损伤修复。     

59. Protectivc effect of melatonin on genetic damage by chemical mutagen and the influence on cell prolife-ration kenetics

Objective: In this study, we observed the effect of melatonin on the frequency of sister chromatid exchange, micronucleus formation of binuclear cell in lymphocyte from human peripheral blood in vitro, micronucleus formation of mouse bone marrow polycychromatic erythrocyte in vivo, which were induced by chemical mutagen, and lymphocyte proliferation kenetics in vitro. Methods: ① Lymphocytes were cultured in vitro in the presence of 0.01,0.10,1.00 mmol/L melatonin, mitomycin C(MMC) (positive control), 0.5% ethanol (negative control)and 0.01,0.10,1.00 mmol/L melatonin plus MMC for 72 h at 37℃±1℃. Lymphocytes were examined for the frequence of SCE, mitotic index, cell proliferation cycle, cell cycle ratio and proliferation index. ② Lymphocytes were cultured in vitro in the presence of 0.01,0.10,1.00 mmol/L melatonin, mitomycin C(MMC) (positive control), 0.5% ethanol (negative control) and 0.01,0.10,1.00 mmol/L melatonin plus MMC for 44 h at 37℃±1℃. Then each culture was given cytochalasin B, which was cultured to 72 h. Binuclear lymphocytes were examined for the micronucleus rate. ③ The mice were administered with 0.1, 1.0,10.0 mg/kg*bw melatonin and distillated water (negative control) respectively for 7 d, then were given melatonin plus cyclophosphamide (CP) (positive control) for 2 d since the eighth day. The rate of micronulclei of mouse bone marrow polycychromatic erythrocyte was examined. Results: ① The frequences of sister chromatid exchange of lymphocytes which were cultured in the presence of 0.01,0.10,1.00 mmol/L melatonin compared with negative control exhibited no statistical significance. ② The SCE of cells treated with melatonin plus MMC compared with positive control were markedly decreased. ③ The mitotic indices of lymphocytes cultured in the presence of 0.10,1.00 mmol/L melatonin were lower than negative control. The proliferation index was significant lower than negative control only in the culture exposed to 1.00 mmol/L melatonin. ④ The proliferation cycle of lymphocyte cultured in the presence of 1.00 mmol/L melatonin exhibited an increase in the percent of cells in their first division, and concomitant significant decrease in their third or later division. which were increased in their second division in cells treated with melatonin of three concentration respectively. The ratio between the first and third or later division, between the second and third or later division of lymphocytes exposed to 1.00 mmol/L melatonin were higher than negative control. ⑤ The micronucleus rates of binuclear lymphocytes treated with 0.01,0.10,1.00 mmol/L melatonin plus MMC were lower than positive control, of which the inhibitory rates of micronuclei were 14.37%, 22.17% and 31.34%, respectively. ⑥ The micronucleus rates of mouse bone marrow polycychromatic erythrocytes exposed to 0.1,1.0,10.0 mg/kg*bw melatonin plus CP were lower markedly than positive control, in which it exhibited a significant and concentration－depended decrease, of which the inhibitory rates of micronuclei were 28.89%, 47.73% and 69.96%, respectively. Conclusion: In vitro assay. It seems that melatonin has not only no genotoxic, but also anti-mutagenic effect on lymphocyte. It can inhibit the increase of frequency of SCE in lymphocyte and micronucleus rate of binuclear lymphocyte induced by MMC, and micronucleus rate of mouse bone marrow induced by CP at some concentiations. It can inhibit the lymphocyte proliferation of mitogen stimulated and has some influence on cell proliferation kenetics at higher concentrations (1.00 mmol/L).     

阿托品对中国仓鼠V79细胞有丝分裂过程的影响

本研究以毒蕈碱型乙酰胆碱受体抑制剂阿托品在离体情况下作用于中国仓鼠Ｖ７９细胞,通过分析Ｖ７９细胞晚末期和早Ｇ１期细胞核细胞质构型,双核细胞频率,探讨了阿托品对哺乳动物离体细胞正常有丝分裂过程的影响。结果发现,阿托品使Ｖ７９细胞的晚末期一早Ｇ１期细胞核和细胞质分裂构型发生显著变化,以核细胞的阿托品可能通过Ｍ型胆碱受体阻断过程而对哺乳动物有丝分裂真实性产生影响。胆碱受体的功能异常可能为非整倍体发生的诱     

麦草粉与绿茶对亚硝化鱼露致微核率增高的抑制作用

应用小鼠骨髓嗜多染经细胞（ＰＣＥ）微核试验方法，研究麦草粉与绿茶对胃癌高发区鱼露径亚硝化后致突变的抑制作用，结果表明：２０％麦草粉，１０％绿茶可降低亚硝化鱼露所致的小鼠微核率增高的作用（Ｐ〈０．０１），将按成分换算后相当于０．０２％ＶＣ的２０％麦草粉干预组和０．００２％ＶＣ的１０％绿茶干预组与０．１％ＶＣ干预对照组比较，微核出现率没有显著差异（Ｐ〉０．０５）。提示麦草粉，绿茶的抑制作用尚与ＶＣ外的     

Synergistic increase in chromosomal breakage within the euchromatin induced by an interaction of the benzene metabolites phenol and hydroquinone in mice

The hematopoietic and carcinogenic effects of benzene may resultfrom an interaction of various benzene metabolites. Followingthe co-administration of phenol and hydroquinone, a synergisticincrease in myelotoxicity and genotoxicity has been observedin the bone marrow of mice. To understand the mechanisms underlyingthese synergistic geno-toxic effects we have studied the originof micronuclei (MN) formed in bone marrow erythrocytes followingthe co-administration of these two metabolites. Phenol and hydroquinonewere administered to male CD-I mice by i.p. injection threetimes at 24 h intervals. The frequency of MN was evaluated inbone marrow cells harvested 24 h following the final dose. Amarked increase in MN was observed in mice co-administered phenoland hydroquinone, which was significantly greater than thatobserved with the individual metabolites. Labeling with theCREST antibody and multicolor fluorescence in situ hybridizationwith the mouse major and minor satellite probes indicated thatboth chromosomal loss and breakage had occurred. The major increasein MN induced by the phenol and hydroquinone combination originatedfrom breakage in the dichromatic region of the mouse chromosomes.The origin of MN in mice co-administered phenol and hydroquinonediffered substantially from that induced by hydroquinone alone,but was almost identical to that seen in MN from benzene-treatedmice. These results strongly support the hypothesis that interactiveeffects among benzene metabolites play an important role inthe genotoxic and carcinogenic effects of benzene.