金不换群三七液对哺乳动物致突变和致畸安全性评价

研究了金不换鲜三七液特殊毒理学效应的致突变性。以小鼠骨髓细胞染色体畸变试验,小鼠睾丸减数分裂染色体畸变及小鼠致畸试验为指标,研究金不换鲜三七液的安全性。结果：（１）小鼠骨髓细胞染色体畸变试验：低,中,高３个剂量组小鼠肌髓细胞染色体畸变率分别为０．７％,０．２％和０．９％,与对照组相比无显著差异。阳性对照组染色体畸变率大大增高。（２）小鼠睾丸减数分别细胞染色体畸变;在本实验条例上,小鼠睾丸细胞染色体     

槲皮素对中国地鼠肺成纤维细胞、小鼠骨髓细胞和小鼠睾丸精母细胞染色体影响的初步研究

目的:研究槲皮素对中国地鼠肺成纤维细胞、小鼠骨髓细胞和小鼠睾丸精母细胞染色体的影响.方法:采用80、40、20、10、5μg/mL 5个剂量组的槲皮素在有或无代谢活化条件下处理体外培养的中国地鼠肺成纤维细胞(CHL)3小时后更换新鲜培养液,恢复生长21小时后收获细胞制片.体内试验以10000、5000、2500mg/kg剂量的槲皮素给ICR小鼠灌胃后取股骨骨髓、两侧睾丸进行制片.观察槲皮素对三种哺乳动物细胞染色体的影响.结果:在有或无代谢活化条件下槲皮素在浓度>10μg/mL均能够诱导CHL细胞染色体断裂和交换等,染色体细胞畸变率显著增加(P<0.01);而槲皮素各剂量组未引起小鼠骨髓细胞染色体断片、交换、畸变细胞率显著增加,亦未引起小鼠睾丸精母细胞染色体断片、易位、畸变细胞率、常染色体单价体、性染色体单价体显著增加.结论:在本试验条件下槲皮素对体外哺乳动物细胞显示出明显致突变性,存在潜在的遗传毒性,对体内哺乳动物体细胞及生殖细胞染色体无明显损伤作用.     

治疗用武汉抗CD3单克隆抗体(WuT_3)的致突变性研究

观察了武汉抗ＣＤ３单克隆抗体（简称ＷｕＴ３）对组氨酸缺陷型鼠伤寒沙门氏菌ＴＡ９７、ＴＡ９８、ＴＡ１００及ＴＡ１０２菌株的回复突变作用。结果显示在５～５０００μｇ／皿的剂量范围内,ＷｕＴ３所致的诱发回复突变菌落数与自发回复突变菌落数之比ＭＲ（Ｒｔ／Ｒｃ）,无论加大鼠肝匀浆,辅酶Ⅱ及葡萄糖６－磷酸（Ｓ－９混合液）或不加Ｓ－９混合液,均不超过２。同时观察了ＷｕＴ３对小鼠骨髓细胞微核率及对人外周血淋巴细胞染色体畸变率的影响,结果显示小白鼠ｉｖＷｕＴ３,每日一次,连续２日,在２５～１００ｍｇ·ｋｇ－１范围内,ＷｕＴ３各剂量组的微核细胞率与溶剂对照组相比均无显著性差异（Ｐ＞０．０５）。而环磷酰胺（ＣＰ）阳性组与溶剂对照组相比有极显著性差异（Ｐ＜０．０１）。ＷｕＴ３在２５～２５０μｇ／瓶的剂量范围内,各剂量组的染色体畸变细胞率与溶剂对照组相比无显著性差异（Ｐ＞０．０５）,而ＣＰ组与溶剂对照组相比有极显著性差异（Ｐ＜０．０１）。三项试验结果均未发现ＷｕＴ３有致突变性作用     

鸡腿蘑对小鼠骨髓细胞的遗传毒性研究

应用小鼠骨髓细胞组织染色单体交换（ＳＣＥ）及微核试验对鸡腿蘑进行遗传毒理检测。结果表明：用鸡腿蘑浸提液处理过的小鼠,其骨髓细胞微核率及ＳＣＥ频率与阴性对照组比较差异不显著（Ｐ〉０．０５）,而与阳性对照组相比,差异极显著（Ｐ〈０．０１）。这表明,鸡腿蘑无致畸变作用。     

蛇毒心脏毒素对动物细胞的遗传损伤和生殖毒性研究

目的 应用眼镜蛇毒心脏毒素（ＣＴＸ）作用于小鼠的骨髓细胞和生殖细胞,以探讨ＣＴＸ对动物体的生殖毒性和遗传毒性。方法 对小鼠腹腔注射不同剂量ＣＴＸ,通过生殖毒性实验和致突变实验,分析孕鼠的胚胎存活率,骨髓细胞和精母细胞的染色体畸变率。结果：ＣＴＸ能影响胎鼠的生长发育,使孕鼠的增重和活胎率均明显地降低（Ｐ〈０．００１）,染色体畸变实验显示ＣＴＸ０．４ｍｇ／ｋｇ剂量上精母细胞多倍体和非整倍体细胞数目增高     

促性腺激素对猪卵丘细胞-卵母细胞复合体体外减数分裂恢复作用的研究

本实验利用猪卵母细胞体外无血清培养技术,选用猪卵泡液中自然存在的次黄嘌呤（ＨＸ）作为卵母细胞自发成熟的抑制剂,研究了促性腺激素对猪卵丘细胞－卵母细胞复合体（ＣＥＯ）减数分裂恢复的具体作用。ＣＥＯ在含有不同浓度的促性腺激素（ＦＳＨ,ｈＣＧ,ＦＳＨ＋ｈＣＧ）的培养液中培养２４ｈ,观察卵母细胞减数分裂恢复（ＧＶＢＤ）情况。实验结果如下：１．ＦＳＨ（１－５００ＩＵ／Ｌ）能够明显刺激ＣＥＯ克服ＨＸ的抑制作用而恢复减数分裂（Ｐ＜０．０５）,该作用具有剂量依赖性;２．ｈＣＧ（１－５００ＩＵ／Ｌ）对ＣＥＯ减数分裂的恢复无明显作用;３．ｈＣＧ（１０－５００ＩＵ／Ｌ）与ＦＳＨ（１０,１００ＩＵ／Ｌ）无协同作用。上述结果表明,猪ＣＥＯ减数分裂的恢复可能主要依赖于ＦＳＨ的作用,该作用能使猪卵丘细胞产生一种或几种阳性因子,作用于卵母细胞,从而克服ＨＸ的抑制作用而恢复减数分裂。ｈＣＧ无明显作用,可能是因为卵丘细胞上没有ＬＨ受体或ＬＨ受体的数量不足     

SOD对骨髓造血祖细胞在4°C条件下保存损伤的防护作用

为了探讨抗氧化剂对造血干细胞在低温条件下损伤的防护作用,将小鼠骨髓细胞置于４℃条件下保存,观察在保养液中加入不同浓度的Ｃｕ、Ｚｎ、ＳＯＤ对细胞死伤的防护效果和马血清对细胞回收率的影响。结果表明,含２０％的马血清保养液中加入ＳＯＤ１．６５Ｕ或０．１６５Ｕ／ｍｌ,保存３天,ＣＦＵ－ＧＭ、ＣＦＵ－Ｅ、ＢＦＵ－Ｅ、ＣＦＵ－Ｍｅｇ、ＣＦＵ－Ｍｉｘ的产率分别为对照组（不加ＳＯＤ）的６．２、２．６、２．９、４．０和５．１倍,明显提高了造血祖细胞的活存率,其中ＣＦＵ－ＧＭ和ＣＦＵ－Ｍｉｘ达到保存前水平。ＳＯＤ的有效作用机理不是对造血祖细胞增殖调控作用,而是防护了细胞的死亡。这可能与其清除过氧自由基的抗氧化作用有密切关系。     

SOD对骨髓造血祖细胞在4℃条件下保存损伤的防护作用

为了探讨抗氧化剂对造血干细胞在低温条件下损伤的防护作用,将小鼠骨髓细胞置于４℃条件下保存,观察在保养液中加入不同浓度的Ｃｕ、Ｚｎ、ＳＯＤ对细胞死务的防护效果和马血清对细胞回收率的影响。结果表明,含２０％的马血清保养液中加入ＳＯＤ１．６５Ｕ或０．１６５Ｕ／ｍｌ,保存３天,ＣＦＵ－ＧＭ、ＣＦＵ－Ｅ、ＣＦＵ－Ｍｅｇ、ＣＦＵ－Ｍｉｘ的产率分别为对照组的６．２、２．６、２．９、４．０和５．１倍。明显提高了造     

厌氧—1号活菌制剂对高脂血症小鼠模型的影响

本实验应用血脂检测及肠道菌群检查法,探讨了对人工高血脂症小鼠模型灌喂厌氧－１号活菌制剂后,小鼠血脂的变化。结果表明：每天给予模型小鼠厌氧－１号菌液（１亿活菌／毫升）０．５毫升,第７天血指即明显下降,与空白对照（自然恢复）组比有显著性差别,血清胆固醇（Ｐ＜０．０１）,降低率为４５．１％;高密度脂蛋白胆固醇（Ｐ＜０．０５）,降低率为４９．１％;甘清三酯（Ｐ＜０．０５）,降低率为１９．２％。到第１４天时血脂均已恢复至正常水平,而自然恢复组小鼠血清胆固醇水平仍比正常对照组略高。     

脐带血清在骨髓造血祖细胞培养中的效应

目的：探讨人脐带清（ＣＢＳ）在骨髓造血祖细胞培养中的效应。方法：用人骨髓细胞进行ＣＦＵ、ＧＭ、ＶＦＵ－Ｅ、ＢＦＵ－Ｅ、ＣＦＵ－ＧＥＭＭ培养。结果：ＣＢＳ能直接刺激骨髓细胞ＣＥＵ－ＧＭ的形成。与血型相同害无关。四人份以上的混合ＣＢＳ（ＭＣＢＳ）,刺激活性高且稳定。１０％ＭＣＢＳ相当于６５．６μｇ／Ｌ ＧＭ－ＣＳＦ、０．２３、０．３、０。．４６ｋＵ／Ｌ ＥｐＯ对ＣＦＵ－ＧＭ、ＣＦＵ－Ｅ、ＢＦＵ－Ｅ、Ｃ     

频繁使用染发剂对小鼠染色体畸变率影响的研究

研究了多次接触７ 种染发剂对不同组小鼠骨髓和生殖细胞染色体畸变率的影响。结果发现, ７ 种染发剂均导致出现较高的染色体畸变率,３ 种能引起小鼠骨髓细胞染色体畸变率显著上升, 其中以粉末状染发剂的影响最为严重。４ 种染发剂对进行生殖细胞染色体畸变实验的小鼠均产生显著影响, 尤以氧化型染发剂最为明显。     

Clastogenicity of carbazole in mouse bone marrow cells in vivo

Clastogenicity of carbazole was evaluated by employing mouse in vivo chromosomal aberration (CA) test. Carbazole administered intraperitoneally (i.p.) at the rate of 25, 50, 100, 150 and 200 mg/kg b.w. to Swiss albino mice in vivo resulted in mitotic depression and induction of chromosomal aberrations. Dose related decrease in mitotic index (MI) and increase in the frequencies of chromosomal aberrations per cell (CAs/cell) and percent abnormal cells were recorded in bone marrow cells. However, statistically significant reduction in MI and increase in CAs/cell and percent abnormal cells were found only for the two higher doses. The results obtained indicate that carbazole or its metabolite, if any, is moderately clastogenic in the bone marrow cells of Swiss albino mice.     

Pathophysiological Scenario of Hematopoietic Disorders: A Comparative Study of Aplastic Anemia,Myelodysplastic Syndrome and Leukemia in Experimental Animals

The conversion of physiology to pathophysiology in hematological disorders viz: aplastic anemia, myelodysplastic syndrome (MDS) and leukemia in murine models was the subject of study in the present programme. Peripheral blood hemogram, spleno-somatic index, bone marrow smear study, cytochemical staining of marrow, cell release kinetics study during marrow explants culture, hematopoietic niche assessment, chromosomal aberration study, plasma membrane stability study of marrow cells, lysosomal membrane and mitochondrial membrane stability study and innate immune parameters were performed in the aplastic anemia, leukemia and MDS mouse model. In bone marrow aplasia, peripheral blood pancytopenia, marrow hypocellularity, decreased marrow cellular viability, deterioration of bone marrow hematopoiesis as well as hematopoietic microenvironment and extramedullary hematopoiesis were noticed. In addition, disruption of mitochondrial and lysosomal membrane integrity along with reduction of innate immune parameters were found in the hematopoietic suppressed condition. Surprisingly, no noticeable chromosomal aberration was found in the aplastic condition. Ineffective marrow hematopoiesis together with the disruption of hematopoietic microenvironment was observed in MDS. Also, extramedullary hematopoiesis, increased marrow cellular death, chromosomal aberration and loss of innate immunity were the common events. During leukemia, the number of functionally and structurally immature cells in the peripheral blood and bone marrow was increased together with malignant conversion of hematopoietic cells in the presence of malignancy supportive stromal microenvironment. Chromosomal aberration, decrease of cell mediated immunity with least mitochondrial apoptotic damage were also found in leukemic condition as well.     

丝裂霉素致小鼠骨髓淋巴细胞遗传损伤及西洋参的干预作用研究

目的:研究西洋参(Panax quinguefolium L)抗突变作用和对细胞增殖的影响.方法:采用小鼠骨髓淋巴细胞有丝分裂指数试验、染色体畸变试验和微核试验,观察西洋参对小鼠骨髓淋巴细胞遗传损伤效应的影响.结果:丝裂霉素(Mitomycin-c MMC)单独作用时,能抑制小鼠骨髓淋巴细胞的增殖(P<0.01),提高小鼠骨髓淋巴细胞的染色体突变(P<0.01)和微核率(P<0.01).西洋参高、中、低剂量组与MMC联合作用时,有丝分裂指数明显比模型组提高(P<0.01),并且均能显著地抑制由于MMC引起的染色体突变,其抑制率分别为68.25%、34.97%和14.29%,同时对MMC诱发的微核率也有明显的抑制效应.结论:西洋参能抑制MMC诱发的染色体畸变率和微核率,促进细胞的增殖能力.     

云锡矿粉诱发大鼠骨髓细胞染色体畸变的研究

云南锡业公司矿工的肺癌发病率高,矿尘中的砷,铁,铅等金属的潜在致癌性已引起了重视(张辅铭等,1985;云南锡业公司劳动防护研究所,华北辐射防护研究所,1982;云锡劳研所流行病室,1982;孙来华等,1986)。鉴于物质的致癌性与致突变性之间有一定的相关性,我们选用5种云锡矿粉,4种金属化合物,研究它们对大鼠骨髓细胞的遗     

Chromosome aberrations and sister-chromatid exchange frequencies in pathology staff occupationally exposed to formaldehyde

Past studies have shown that formaldehyde is mutagenic in microbial tests and Drosophila and causes chromosomal aberrations in cultured mammalian cells. Chromosomal analysis of bone marrow cells and spermatocytes from exposed laboratory animals has failed to show any genotoxic effect. Information on individuals occupationally exposed is limited and there is no evidence to date that formaldehyde can induce chromosome damage at occupational levels of exposure. This study examines the chromosome aberration and sister-chromatid exchange frequencies in lymphocytes from a group of 6 pathology workers and 5 unexposed controls. No detectable differences could be found between the groups in either chromosomal aberration induction or sister-chromatid exchange frequencies.     

Synaptonemal complex analysis of B-chromosome behavior in meiotic prophase I in the East-Asiatic mouse Apodemus peninsulae (Muridae, Rodentia)

The mitotic and meiotic chromosomes of four male East-Asiatic mice, Apodemus peninsulae, having three to seven chromosomes in addition to the standard karyotype (2n = 48), were investigated. B-chromosomes were represented by medium-sized metacentric and dotlike chromosomes. Mosaicism of bone marrow cells due to a numerical variation of accessory chromosomes was established for the males examined. Capacity of B-chromosomes to form axial elements and synaptonemal complexes in meiotic prophase I was revealed by electron microscopy. The occurrence of univalents of different morphology, bivalents, and multivalents, corresponding to B-chromosomes, was demonstrated. An increase in the number of B-chromosomes was found in spermatocytes at zygotene-pachytene relative to the number in bone marrow cells, which may be evidence of B-chromosome accumulation in the germ cell line of the East-Asiatic mouse.     

Clastogenic effects of acrylamide in mouse bone marrow cells

Acrylamide, known to induce dominant-lethal mutations (Shelby et al., 1986; Smith et al., 1986) and heritable translocations (Shelby et al., 1987) in rodent germ cells, was hitherto a questionable clastogen in rodent bone marrow (Shiraishi, 1978). Therefore, it was tested for chromosomal aberrations in mouse bone marrow cells, spermatogonia and by the micronucleus test. The intraperitoneally injected doses ranged from 50 to 150 mg/kg. In the chromosomal bone marrow test and the micronucleus assay positive results were obtained with acrylamide, and in the latter test the effect increased linearly with dose. Chromosomal aberrations were not induced in differentiating spermatogonia by the acute acrylamide treatment. Cisplatin was used as a positive control and gave the expected positive response in all 3 tests. The present results demonstrate that acrylamide is no exception among clastogens. It breaks chromosomes not only in mammalian germ cells but also in somatic cells.     

Clastogenic effects of hydroquinone: induction of chromosomal aberrations in mouse germ cells

The clastogenic activity of hydroquinone (HQ) in germ cells of male mice was evaluated by analysis of chromosomal aberrations in primary spermatocytes and differentiating spermatogonia. In the first experiment with treated spermatocytes the most sensitive stage of meiotic prophase to aberration induction by HQ was determined. Testicular material was sampled for microscopic analysis of cells in diakinesis-metaphase I at 1, 5, 9, 11, and 12 days after treatment with 80 mg/kg of HQ, corresponding to treated diplotene, pachytene, zygotene, leptotene and preleptotene. The frequencies of cells with structural chromosome aberrations peaked at 12 days after treatment (p less than 0.01). This indicates that the preleptotene when DNA synthesis occurred was the most sensitive stage of meiotic prophase. In the second experiment the dose response was determined 12 days post treatment by applying 2 additional doses of 40 mg/kg and 120 mg/kg. The clastogenic effects induced by 40 and 80 mg/kg were significantly different from the controls (p less than or equal to 0.01) and higher than the results obtained with 120 mg/kg of HQ. A humped dose-effect relationship was observed. In a third experiment the same doses were used to analyse chromosomal aberrations in dividing spermatogonia of mice 24 h after treatment with HQ. All the administered doses gave results statistically different from the control values (p less than or equal to 0.01) and the data were fitted to a linear equation. HQ was found to be clastogenic in male mouse germ cells. It is concluded that the clastogenic effect in male germ cells is of the same order of magnitude as in mouse bone marrow cells.     

Lack of clastogenic effects of irradiated glucose in somatic and germ cells of mice

The clastogenic ability of irradiated glucose was evaluated using the micronucleus test in bone marrow cells and the chromosomal aberration assay in the spermatogonial cells of mice. Glucose was irradiated with 0.2, 2.0, 20 and 50 kGy of gamma-rays and administered to mice for various periods. No evidence of mutagenic effects was observed in somatic or germ cells.