V2O5对小鼠胚胎及其母体不同组织细胞致突变性的研究

本研究选用昆明种小鼠,在妊娠6～14天,每天腹腔给予0、0.2、1.0和5.0mg/kg的V_2O_5,末次给药后15～18小时,分析母体及胚胎细胞的微核和SCE频率。结果:V_2O_5对SCE频率均无显著影响(P>0.05);但诱导了胎肝及母鼠脾脏、骨髓PEC的微核率的显著增加(P<0.05)。这表明,V_2O_5不仅对成体确具诱变性,而且还能透过胎盘,诱发胚胎细胞的染色体损伤。MNT结果还揭示:胎肝和孕鼠脾脏对化学物质的微核诱导作用较骨髓敏感;当MNT结果在界值附近时,最好采用AO染色法。     

硒对酱油诱发小鼠骨髓细胞SCE的抑制作用

本实验结果表明，喂酱油能诱发小鼠骨髓细胞姊妹染色单体交换率的增高，差异极其显著；自由饮用４ｐｐｍ的亚硒酸钠可抑制酱油诱发ＳＣＥ的增高，差异差异极其显著；提示硒作为一种潜在的食品在抗突变和抗癌添加剂的可能性。     

汽车尾气对小鼠骨髓细胞的致突变性

目的探讨汽车尾气对小鼠骨髓细胞的致突变性。方法健康昆明种小鼠100只,随机分10组,雌雄各半。用汽车尾气分别染毒15、30、45、60d后,观察小鼠骨髓细胞微核率和姐妹染色单体交换率变化,并与正常饲养组小鼠骨髓细胞进行比较。结果各染毒组与对照组之间的微核率、姐妹染色单体交换率有差异,除15d组和对照组的差异无显著性(P>0.05)外,其他各组和对照组比较,差异均有显著性(P<0.01);且染毒时间对小鼠骨髓细胞的致突变影响呈正相关。结论汽车尾气对小鼠骨髓细胞有致突变性。     

二氧化硫吸入诱发小鼠骨髓细胞染色体畸变的效应

目的 为了了解二氧化硫（SO2）吸入对小鼠骨髓细胞染色体畸变（CA）的诱发作用。方法 以不同浓度SO2气体对小鼠熏气,随后分析小鼠骨髓细胞分裂指数和染色体畸变（CA）率和畸变细胞率。结果 SO2可诱发细胞CA率和畸变细胞率显著增高,且呈明确的剂量－反应关系。在SO2不同浓度（0、14、28、56及84ng/m^3）染毒条件下,小鼠骨髓细胞畸变细胞率（％）分别为1．81、3．00、3．58、4．26、4．86。SO2在低浓度下主要诱发染色单体型畸变,在高浓度下既可引起染色单体畸变,又可引起染色体型畸变。SO2可引起骨髓细胞分裂指数显著降低。结论 吸入SO2气体可抑制小鼠骨髓细胞分型,引起染色体畸变,SO2是染色体断裂剂和基因毒性因子。长期接触环境低浓度SO2污染,有引起接触人群体内细胞遗传物质损伤的潜在危险。     

硝酸镧染毒对小鼠骨髓细胞微核率的影响

目的研究硝酸镧染毒对小鼠骨髓细胞微核率的影响。方法将21日龄昆明种小鼠随机分为9组,每组12只,分别腹部皮下注射不同剂量的硝酸镧溶液(10、50、100、200、300、400、500mg/kg),阴性对照组给予蒸馏水,阳性对照组给予环磷酰胺,每天1次,连续7d,观察小鼠骨髓细胞微核率及小鼠体重。结果300、400、500mg/kg组小鼠增重低于阴性对照组,差异有显著性(P<0.05)。100、200、300、400、500mg/kg组小鼠骨髓细胞微核率高于阴性对照组(P<0.05)。随染毒剂量增加,小鼠骨髓细胞微核率呈上升趋势(r=0.9223P<0.05)。结论硝酸镧具有一定遗传毒性。     

Effect of the antifertility agent, gossypol acetic acid, on the metabolism and testosterone secretion of isolated rat interstitial cells in vitro

Gossypol acetic acid is a polyphenolic compound present in the seed of cotton plants. Its antifertility activity by inhibition of spermatogenesis was proven in a large group of animals, including man. In the present study, the direct effect of gossypol acetic acid on collagenase isolated rat I-cells (interstitial cells) was investigated. It was shown that gossypol acetic acid depressed significantly the metabolic rate of the cells. Glucose utilization was abolished by a starting dose of 100 μg/ml. Oxygen consumption of I-cells was reduced even at a smaller dose of gossypol (50 μg/ml). At these doses, the vitality of the cells remained (proven by trypan blue exclusion test). slightly 3 β-Hydroxysteroid dehydrogenase (3 β-HSD) histochemical stain was decreased. Increasing doses of gossypol caused a marked decrease in the vitality of I-cells and a dramatic drop in histochemical stain for 3 β-HSD. The pH of the medium was not changed at any dose of treatment. In cultures of I-cells not stimulated by hCG, gossypol did not affect the tonic slow release of testosterone. Thus, gossypol acetic acid has a direct inhibitory effect on isolated rat I-cells, depressing cell metabolism. The failure of some of the other groups to show such an effect, especially in vivo, can be attributed to differences in the dose of treatment and strain of animals.     

表没食子儿茶素没食子酸酯抗突变的实验研究

目的 研究表没食子儿茶素没食子酸酯（ＥＧＣＧ）抗突变作用。方法 以昆明纯种小鼠的骨髓细胞为实验材料,用公认的诱变剂环磷酰胺（ＣＰ）诱发的微核（ＭＮ）率和姐妹杂色单体互换（ＳＣＥ）频率为指标,研究ＥＧＣＧ对ＣＰ诱导小鼠骨髓细胞ＭＮ和ＳＣＥ的影响。结果 ＥＧＣＧ对ＭＮ和ＳＣＥ均具明显抑制作用。结论 ＥＧＣＧ具有抗突变性和潜在的预防肿瘤的作用。     

电离辐射和丝裂霉素C诱导交叉适应性反应

目的 探讨低剂量电离辐射和低浓度丝裂霉素C之间的交叉适应性反应规律。方法 以人淋巴细胞、小鼠骨髓细胞为实验材料，分别用低剂量X射线或低浓度丝裂霉素C作适应性处理，再用高浓度丝裂霉素C或大制量X射线作攻击性处理。观察人淋巴细胞染色体畸变、微核、SCE，小鼠骨髓细胞染色体畸变。结果 人淋巴细胞染色体畸变、SCE，小鼠骨髓细胞染色体畸变分别呈现出低剂量X射线与低浓度丝裂霉素C的交叉适应性反应。结论 无论在离体条件下，还是在哺乳动物体内，低剂量辐射与低浓度丝裂霉素C之间存在着相互的交叉适应性反应现象。     

酱油对小鼠骨髓细胞的致突变作用

本文应用昆明种小鼠进行体内实验,用细胞遗传学的三个指标,即小鼠骨髓嗜多染红细胞(PCE)微核率、染色体畸变(CA)率和姊妹染色单体交换(SCE)率检测酱油的致变性。结果表明,给予小鼠灌喂酱油能诱发小鼠骨髓PCE微核率、CA率和SCE率的增高。实验组的三个指标与阴性对照比较,有高度显著差异(P>0.01),并呈剂量反应关系。对煮沸处理和未煮沸处理的酱油进行比比较,差异无显著性(P>0.05),表明酱油中的致变物和前致变物对热较为稳定,结果证明,酱油对哺乳动物体内细胞具有和对细菌一样的致变性。     

四氯化碳对雄性小鼠的遗传毒性

目的检测环境污染物四氯化碳的诱变活性,评价其可能的潜在遗传毒性。方法21只雄性昆明种小鼠随机分成7组,每组3只,其中1组为对照组,其余6组采用腹腔注射的方法,分别用5、15、25mg/kg四氯化碳进行染毒24h和48h分别进行精子畸形试验和小鼠股骨骨髓嗜多染红细胞(PCE)微核试验,然后每组观察5000个精子计算精子畸变率;每组观察5000个股骨骨髓PCE细胞,计算微核率。结果染毒小鼠的精子有明显的畸变效应,小鼠股骨骨髓PCE细胞的微核率和精子畸变率明显高于对照组(P<0.01)。结论四氯化碳对小鼠生殖细胞和血红细胞有遗传毒性作用。     

香烟烟雾对孕鼠和胎鼠的遗传毒性研究

研究了昆明种小鼠在孕期被动吸烟对孕鼠和胎鼠的遗传毒理效应。结果发现香烟烟雾可显著诱导孕鼠骨髓细胞染色体畸变（ＣＡ）率和ＳＣＥ率，胎鼠肝嗜多染红细胞微核细胞率ＭＮＣＦ（Ｐ＜０．０５）。如果被动吸烟孕鼠同时服用苯巴比妥钠以诱导肝脏混合功能氧化酶系，则孕鼠和胎鼠的ＣＡ率，ＳＣＥ率和ＭＮＣＦ都明显升高（Ｐ＜０．０５）。提示孕期被动吸烟对母、胎双方均可造成遗传物质损伤。苯巴比妥钠诱导的高活性混合功能氧化酶系对烟雾中遗传毒性物质可起代谢活化作用。     

Antifertility and endocrine activities of gossypol in rodents

Reversible male antifertility activity was obtained with orally administered gossypol acetic acid in rats at 20 mg/kg/day and in hamsters at 10 mg/kg/day but not in mice at dosages up to 40 mg/kg/day. An increased number of degenerating spermatocytes was found in the testicular tubular lumens of rats. Pigment-laden cells containing an intracytoplasmic lipofuscin-like material were noted in the testis and epididymal interstitium in rats and mice. Gossypol was also tested in the female for effects on ovulation and pregnancy. Gossypol did not inhibit ovulation in the rat at dosages up to 80 mg/kg/day but did cause 90% inhibition of pregnancy in mice treated with 80 mg/kg/day during the first two weeks of pregnancy. In several standard endocrine bioassays, gossypol did not demonstrate estrogenic, antiestrogenic, androgenic or antiandrogenic activities, but it did potentiate the androgenicity of methyltestosterone.     

Genotoxicity studies of rodents exposed to coal dust and diesel emission particulates

Genotoxicity studies with mice and/or rats have been conducted to evaluate the potential mutagenic hazard associated with exposures of coal miners to diesel emission particulates (DEP) and/or coal dusts (CD). Rats and mice were exposed to filtered air, DEP, and/or CD for periods ranging from 3 months to 2 years. Levels of respirable particulates were maintained at 2 mg/m3 in all exposed groups. DEP and/or CD were collected in the inhalation chambers in which animals were exposed. Urine samples were collected for 5 consecutive days from rats exposed to DEP and/or CD for 3, 6, and 24 months. The particulate samples extracted with dichloromethane and the urine samples concentrated with XAD-2 columns were analyzed for mutagenic activity by the Ames Salmonella/microsome assay system. Peripheral blood lymphocytes from rats exposed for 3 months were analyzed for sister chromatid exchanges (SCE). The femur bone marrow cells from rats exposed for 24 months and mice exposed for 6 months were analyzed for micronuclei in both polychromatic and normochromatic erythrocytes. The results indicate that the solvent extract of DEP was mutagenic, while no mutagenic activity was found for the CD extract. Combination of CD and DEP did not show any synergistic effect. No mutagenic activity was found for urine samples from rats exposed to DEP and/or CD for up to 2 years. A slight increase in the micronucleated polychromatic erythrocytes over the control level was found in mice exposed to DEP and DEP plus CD for 6 months but the increase was not statistically significant. No increase in micronuclei was detected in rats exposed for 24 months. The frequencies of SCE in the peripheral lymphocytes of the 3-month-exposed rats were similar for control and DEP plus CD-exposed groups.     

Influence of seed extract of Syzygium Cumini (Jamun) on mice exposed to different doses of gamma-radiation

The radioprotective activity of the hydroalcoholic extract of jamun seeds (SCE) was studied in mice exposed to different doses of gamma radiation. The mice were injected with 0, 5, 10, 20, 40, 60, 80, 100, 120, 140 or 160 mg/kg body weight of SCE, before exposure to 10 Gy of gamma radiation, to select the optimum dose of radiation protection. The 80 mg/kg SCE was found to offer highest protection, therefore, further studies were carried out using this dose. The drug was more effective when administered through the intraperitoneal route at equimolar doses than the oral route. Since higher survival was observed for the i.p. route (50%), than the oral route (29.2%), all other studies were carried out by injecting SCE intraperitoneally. The mice treated with 80 mg/kg body weight SCE intraperitoneally before exposure to 6, 7, 8, 9, 10 and 11 Gy of gamma radiation showed reduction in the symptoms of radiation sickness and mortality at all exposure doses and caused a significant increase in the animal survival when compared with the concurrent double distilled water (DDW) + irradiation group. The SCE treatment protected mice against the gastrointestinal as well as bone marrow deaths and the DRF was found to be 1.24.     

Radioprotective effects of hawthorn fruit extract against gamma irradiation in mouse bone marrow cells

The radioprotective effect of hawthorn (Crataegus microphylla) fruit extract against genotoxicity induced by gamma irradiation has been investigated in mouse bone marrow cells. A single intraperitoneal (ip) administration of hawthorn extract at doses of 25, 50, 100 and 200 mg/kg 1h prior to gamma irradiation (2 Gy) reduced the frequencies of micronucleated polychromatic erythrocytes (MnPCEs). All four doses of hawthorn extract significantly reduced the frequencies of MnPCEs and increased the PCE/PCE+NCE ratio (polychromatic erythrocyte/ polychromatic erythrocyte + normochromatic erythrocyte) in mice bone marrow compared with the non drug-treated irradiated control (p < 0.02-0.00001). The maximum reduction in MnPCEs was observed in mice treated with extract at a dose of 200 mg/kg. Administration of amifostine at dose 100 mg/kg and hawthorn at dose 200 mg/kg reduced the frequency of MnPCE almost 4.8 and 5.7 fold; respectively, after being exposed to 2 Gy of gamma rays, compare with the irradiated control group. Crataegus extract exhibited concentration-dependent activity on 1,1-diphenyl 2-picrylhydrazyl free radical showing that Crataegus contained high amounts of phenolic compounds and the HPLC analysis determined that it contained chlorogenic acid, epicatechin and hyperoside. It appeared that hawthorn extract with antioxidant activity reduced the genotoxicity induced by gamma irradiation in bone marrow cells.     

Protection against radiation induced hematopoietic damage in bone marrow of Swiss albino mice by Mentha piperita (Linn)

The protective effects of Mentha piperita (Linn) extract against radiation induced hematopoietic damage in bone marrow of Swiss albino mice have been studied. Mice were given either double distilled water or leaf extract of M. piperita orally (1 g/kg b.wt./day) once a day for three consecutive days, and after 30 min of treatments on the third day were exposed to 8 Gy gamma radiation. Mice were autopsied at 12, 24, 48 hrs and 5, 10 and 20 days post-irradiation to evaluate the percentage of bone marrow cells, frequency of micronuclei and erythropoietin level in serum. An exposure to gamma radiation resulted in a significant decline in the number of bone marrow cells such as leucoblasts, myelocytes, metamyelocytes, band/stab forms, polymorphs, pronormoblasts and normoblasts, lymphocytes, and megakaryocytes. Pretreatment with leaf extract of M. piperita followed by radiation exposure resulted in significant increases in the numbers of leucoblasts, myelocytes, metamyelocytes, band/stab forms, polymorphs, pronormoblasts and normoblasts, lymphocytes, and megakaryocytes in bone marrow as compared to the control group. Pretreatment with leaf extract of M. piperita followed by radiation exposure also resulted in significant decreases in micronucleus frequencies in bone marrow of Swiss albino mice. A significant increase in erythropoietin level was observed at all the studied intervals in leaf extract of M. piperita pretreated irradiated animals as compared to control animals (radiation alone). The results of the present investigation suggest the protective effects of leaf extract of M. piperita against radiation induced hematopoietic damage in bone marrow may be attributed to the maintenance of EPO level in Swiss albino mice.     

苦瓜对环磷酰胺致突变活性的影响

Inhibitory effects of balsam pear on the mutagenic activity of cyclophosphamide were studied in the cells of bone marrow of mouse in vivo. It was found that balsam pear juice itself showed no effect on the incidence of sister chromatid exchanges (SCE) and of micronuclei (MN) on the cells of bone marrow. But balsam pear juice reduced the incidence of SCE (from 29.1 times/cell to 13.27-28.38 times/cell) and MN (from 60.0% to 27.0%-50.0%) induced by cyclophosphamide respectively. The inhibitory effects showed a dose-dependent relation, which was statistically significant.     

Selective toxicity of gossypol against epithelial tumors and its detection by magnetic resonance spectroscopy

The antitumor toxicity of gossypol was measured in 6 human carcinoma cell lines and compared with its toxicity against human bone marrow stem cells. Marrow cells were more resistant than any of the tumor cell lines, and tumor cell sensitivity depended on the content of intracellular LDH-M. [31P]-Magnetic resonance spectroscopy showed decline in tumor ATP levels occurring within 24 hours of treatment, suggesting that this non-invasive technique may serve as an early biochemical monitor of gossypol toxicity.     

骨髓间充质干细胞对异基因骨髓移植后GVHD和生存率的影响

目的　观察骨髓间充质干细胞 (BMMSC)对急性淋巴细胞白血病 (ALL)小鼠异基因骨髓移植 (allo -BMT)后移植物抗宿主病 (GVHD)和生存率的影响。方法　建立ALL小鼠动物模型 ,对其进行allo -BMT的同时 ,静脉输注体外培养的供鼠BMMSC ,同时设立单纯allo -BMT对照组。流式细胞仪检测受鼠CD4+ 、CD8+ T细胞亚群的差异 ;观察受鼠发生GVHD一般反应及病理学变化 ;记录受鼠存活时间。结果　BMMSC减少受鼠CD4+ T细胞的同时增加CD8+ T细胞 ;推迟GVHD发生的时间 ;明显延长ALL小鼠allo -BMT后的生存时间 (P <0 0 5或P <0 0 1)。结论　BMMSC能抑制ALL小鼠allo -BMT后GVHD的发生 ,但同时具有一定程度的GVL作用。     

Effects of gossypol on the kidney with special emphasis on potassium (K) excretion

The overall and renal toxicity of racemic gossypol acetic acid was assessed in 6 mongrel dogs. Oral racemic gossypol acetic acid was given orally at doses increasing from 10 to 40 mg/d for a total of 6 weeks in 3 female dogs and from 40 to 80 mg/d for a total of 4 weeks in 3 male dogs. The animals were then sacrificed. Drug tolerance was excellent. Pathological examination of the liver and heart was normal. Renal function remained normal. The renal excretion of K, Mg, phosphate and acid remained normal. Serum K remained within the range appropriate for animals on a K-free diet. Pathological examination of the kidney disclosed mild proximal tubule vacuolization similar to that observed in animals on a K-free diet and small brownish pigment deposits in a few tubular cells. Spermatogenesis was arrested in the testes of one of the 3 male dogs. We conclude that short exposure to 10 to 80 mg/day of gossypol does not result in detectable toxic effect. Neither significant hypokalemia nor a tubular K leak were observed.