环磷酰胺对小鼠外周血微核红细胞率的影响

骨髓多染红细胞微核试验(MT)具有简易、快速和敏感的特点,但存在着不能结合亚慢性或慢性毒性试验观察微核细胞率动态变化的缺点。本文试图以外周血微核正染红细胞千分率(MNNCE率)及微核多染红细胞千分率(MNPCE率)为指标,检测已知断裂剂环磷酰胺(CP)的断裂作用,弥补MT的不足,报道如下。取健康雌雄小鼠各20只,按性别随机分入CP5、10、20和40mg/kg四个剂量组和一个生理盐水对照组。动物隔天腹腔注射CP或生理盐水一次共八次。定     

细菌防护液对小鼠辐射前后骨髓嗜多染红细胞微核率的影响

细菌防护液是我们研制的一种预防辐射损伤的药物,它能提高照射小鼠的存活天数。本实验以观察小鼠骨髓嗜多染红细胞微核率为指标,研究细菌防护液的遗传毒性作用,并观察对辐射后小鼠微核率的影响。以蒸馏水作阴性对照,环磷酰胺作阳性对照,细菌防护液为实验组。给小鼠每天灌胃０５ｍｌ,连续５ｄ。结果显示,细菌防护液未能造成细胞突变,说明它对小鼠骨髓嗜多染红细胞没有遗传毒性作用。给小鼠灌胃一定剂量的细菌防护液,然后用６０Ｃｏγ射线１次性照射小鼠,总剂量为６０Ｇｙ。结果显示,照射可以使骨髓嗜多染红细胞微核率增加,如…     

桉叶油毒性及其对环磷酰胺致小鼠骨髓微核及精子畸形的保护作用

目的探讨桉叶油对环磷酰胺(CP)致小鼠遗传毒性的保护作用。方法①毒性实验:小鼠ig给予桉叶油1700,1750,1800,1850和1900mg·kg-1,检测桉叶油的半数致死量(LD50)。另小鼠分别ig给予桉叶油100,200和400mg·kg-1及花生油(阴性对照)组,每天1次,连续5d。阳性对照组ip给予CP40mg·kg-1,每天1次,共给2d。检测小鼠骨髓嗜多染红细胞微核率。30只雄性小鼠,分别ig给予按叶油100,200和400mg·kg-1和花生油,阳性对照组ip给予CP40mg·kg-1,每天1次,连续5d。观察小鼠精子畸形率。②保护作用实验:小鼠按照如下分组给药:CP+桉叶油400,200和100mg·kg-1,花生油+CP,CP组。第4天与阳性对照组一起ip给予CP40mg·kg-1,每天1次。第5天给药后测定小鼠骨髓微核率。30只雄性小鼠按分组,第6天起与阳性对照组一起每天ip给予CP40mg·kg-1,连续5d,实验共10d。测定小鼠精子畸形率。结果①毒性实验:桉叶油的LD50为1824.01mg·kg-1,95%可信限为(1799.48～1851.19)mg·kg-1。桉叶油对小鼠骨髓嗜多染红细胞微核率和精子畸形率无影响。②保护作用实验:桉叶油100,200和400mg·kg-1组的微核率和精子畸形率明显低于未ig给予桉叶油的CP诱发的微核率和精子畸形率(P<0.05)。结论桉叶油对小鼠无明显的遗传毒性,可降低CP所致小鼠骨髓嗜多染红细胞微核率和精子畸形率。     

低纯度熊果酸对小鼠致变性及其拮抗作用的研究

目的研究熊果酸(Ursolic Acid,UA)的致突变作用及其拮抗作用。方法采用小鼠骨髓嗜多染红细胞微核实验、小鼠染色体畸变实验、小鼠精子畸形实验和改进的小鼠骨髓嗜多染红细胞微核实验、染色体畸变实验、小鼠精子畸形实验,通过检测骨髓嗜多染红细胞微核率、染色体畸变率和精子畸形率来研究熊果酸的致突变性和抗突变性。结果熊果酸各致突变实验组(HUA、MUA、LUA)与阳性对照组(环磷酰胺,CP)相比,差异有统计学意义(P0.05),表明熊果酸没有致突变性;熊果酸抗突变实验组(HUA+CP、MUA+CP和LUA+CP)与阳、阴性对照组相比,差异有统计学意义(P0.05),表明熊果酸可降低环磷酰胺诱发的细胞微核、染色体畸变率和精子畸形率。结论在本试验条件下,熊果酸无致突变作用,具有一定的拮抗作用。     

迷迭香酸对γ射线致小鼠骨髓嗜多染红细胞微核的保护作用

目的研究迷迭香酸对γ射线致小鼠骨髓嗜多染红细胞微核的保护作用。方法以骨髓嗜多染红细胞微核形成率为观测指标,C57BL/6J小鼠经60Coγ射线1～3 Gy照射24 h后观察骨髓嗜多染红细胞微核发生率的变化以选择合适的照射剂量;C57BL/6J小鼠经60Coγ射线2Gy照射后不同时间观察骨髓嗜多染红细胞微核发生率的变化以选择照射后取骨髓的时间;2 Gy照射前经迷迭香酸处理的C57BL/6J小鼠照后24 h观察骨髓嗜多染红细胞微核发生率的变化,以确定迷迭香酸对小鼠微核保护作用的剂量效应与时间效应。结果 2 Gy照射24 h后小鼠骨髓嗜多染红细胞微核发生率增加比较明显,适合作为小剂量照射条件;照射后24 h或48 h骨髓嗜多染红细胞微核发生率增加比其他时间明显;经迷迭香酸100 mg/kg连续7次处理后的受照射小鼠骨髓细胞中,微核发生率（6.50‰）明显低于单纯照射组（23.65‰）。结论迷迭香酸对γ射线致骨髓嗜多染红细胞微核具有保护作用。     

重质芳烃的致突变性

目的与方法　用Ａｍｅｓ试验、小鼠骨髓嗜多染红细胞微核试验、人外周血淋巴细胞姐妹染色单体交换 (ＳＣＥ)试验以及小鼠精子畸形试验对重质芳烃进行了致突变性研究。结果　重质芳烃无移码突变和碱基置换效应 ;微核试验显示在316～ 15 80ｍｇ ｋｇ剂量范围内 ,小鼠骨髓嗜多染红细胞微核率显著增加 (6 2 5‰～ 10 0 0‰ ,与阴性对照组的 2 38‰比较 ,Ｐ <0 .0 1) ;ＳＣＥ试验结果显示在活化系统 (Ｓ9混合液 )存在的条件下 ,人外周血淋巴细胞ＳＣＥ频率较对照组显著增高 (在0 5ｍｇ ｍｌ及 5ｍｇ ｍｌ剂量组分别为 3 48及 4 84,对照组为1 …     

来氟米特3-甲基异构体对小鼠的致突变实验

目的:观察来氟米特3-甲基异构体的致突变作用。方法:取小鼠分为空白对照组、溶剂对照组、阳性对照组和来氟米特3-甲基异构体受试药不同剂量组;分别采用Ames实验观察每皿回变菌落数、小鼠骨髓嗜多染红细胞微核实验观察微核率、小鼠精子畸变实验观察精子畸变率。结果:Ames实验中受试药各剂量组回变菌落数均未超过溶剂对照组回变菌落数的2倍,实验结果为阴性;小鼠骨髓嗜多染红细胞微核实验及小鼠精子畸变实验中受试药各剂量组与空白对照组比较,微核率及精子畸变率无明显差异(P>0.05)。结论:在本次实验条件下,来氟米特3-甲基异构体未显示有致突变作用。     

多环芳烃对金属硫蛋白缺欠小鼠微核及红细胞的影响

目的：观察两种致癌性多环芳烃化合物二甲基苯蒽（DMBA）和苯并（a）芘（BaP）对小鼠髓多染红细胞微核发生和血液循环中红细胞数量的时相影响以及金属硫蛋白的可能拮抗作用。方法：选用雄性金属硫蛋白（MT）基因敲除的转基因小鼠[MT(-/-)]和野生型小鼠[MT( / )]。在DMBA和BaP各50mg/kg1次腹腔注射染毒后24、48、72和144h，观察动物骨髓多染红细胞中的微核细胞发生率和外周血液循环中红细胞数量的变化。结果：DMBA和BaP均能引起两种小鼠骨髓多染红细胞微核发生增加和外周血液循环中红细胞数量减少。DMBA诱导微核发生的高峰在48h。在同种小鼠内DMBA诱导的微核细胞发生率大于BaP。在DMBA染毒48和72h后MT（－／－）小鼠的微核细胞率明显大于MT（＋／＋）小鼠，而在BaP染毒后两种小鼠之间差异无显著性。在DMBA染毒24h后MT（－／－）小鼠的红细胞数比染毒前明显减少。结论：在该研究 条件下，缺乏MT的小鼠的骨髓多染红细胞微核更易被DMBA诱导和发生红细胞数量减少。提示MT具有一定保护DMBA所致遗传损伤和红细胞系统损伤的功能。     

胸腺肽对环磷酰胺诱发小鼠骨髓细胞微核率的影响

观察了胸腺肽（TP）对环磷酰胺（CP）诱发小鼠骨髓嗜多染红细胞微核率（PCEMN）的抑制作用。结果表明，在iPCP75mg／kg前2、3h和给予后1、2、3h将TP100mg／kgip，小鼠，可明显抑制PCEMN。由此可见，TP具有保护CP可遗传物质的损伤作用。     

油松花粉遗传毒性研究

目的 探讨油松花粉的遗传毒性,为其应用提供安全性毒理学评价依据.方法 用鼠伤寒沙门细菌营养缺陷型突变株TA97(a)、TA 98、TA 100和TA 102,采用平皿掺入法进行Ames实验,将实验分为加和不加代谢激活系统S9 2组平行实验.受实物设5个剂量组(0.008、0.040、0.200、1.000、5.000 mg/皿).应用小鼠骨髓嗜多染红细胞微核实验,检测小鼠骨髓嗜多染红细胞微核率;利用小鼠精子畸形实验,观察不同浓度的油松花粉致小鼠精子畸形的数目.结果 在Ames实验中,油松花粉各剂量组引起的回变菌落数未超过对照组自发回变菌落数的1倍以上;小鼠骨髓嗜多染红细胞微核实验显示,油松花粉3个剂量组的微核发生率均在正常范围内,与阴性对照组比较差异无显著性(P＞0.05),与阳性对照组比较差异显著(P＜0.05);小鼠精子畸形实验显示,油松花粉3个剂量组的精子畸形率均在正常范围内,与阴性对照组比较差异无显著性(P＞0.05),与阳性对照组比较差异显著(P＜0.05).结论 油松花粉对所实菌株、小鼠体细胞及生殖细胞无诱变性.     

Chemoprotective effects of captopril against cyclophosphamide-induced genotoxicity in mouse bone marrow cells

The protective effects of captopril (CAP) against toxicity induced by cyclophosphamide (CP) in mice were investigated using the micronucleus assay for anticlastogenic activity in mouse bone marrow cells and liver glutathione (GSH) content. A single intraperitoneal (i.p.) injection of CAP at 50, 100, and 200 mg/kg 1 h prior to cyclophosphamide (50 mg/kg) reduced the frequency of micronucleated polychromatic erythrocytes (MnPCEs). All three doses of CAP significantly reduced the frequency of MnPCEs in mouse bone marrow compared to the group treated with CP alone (P<0.0001–0.01). CP significantly depleted the GSH content in liver but the application of CAP at a dose of 100 mg/kg 1 h before CP treatment repleted the GSH content. CAP exhibited concentration-dependent antioxidant activity, scavenging >96% of the 1,1-diphenyl-2-picryl hydrazyl free radicals when used at a concentration of 0.2 mM. It appears that CAP, due to its antioxidant activity and by increasing GSH levels, can modulate the reduced cellular thiol content induced by CP and reduce the genotoxicity of CP in bone marrow cells.     

碘伏消毒液毒理学试验研究

目的研究碘伏（AEO-1）消毒液使用的安全性。方法采用小鼠急性经口毒性、小鼠骨髓细胞微核、一次破损皮肤刺激、多次完整皮肤刺激、急性眼刺激、一次阴道黏膜刺激及亚急性毒性等试验。结果该碘伏消毒液LD50大于5000mg／kg,属实际无毒,小鼠骨髓细胞微核试验为阴性,碘伏消毒液原液对家免皮肤、眼及阴道黏膜刺激的刺激指数均为0,均属无刺激性;亚急性毒性试验,当高剂量组为1．0g／kg时,各项检测指标均未观察到异常变化。结论提示AEO-1为载体的碘伏消毒液在使用浓度下是安全的。     

Protective effects of 4-nerolidylcatechol against genotoxicity induced by cyclophosphamide.

In the present work we evaluated both the mutagenicity and antimutagenicity of the Pothomorphe umbellata root extract (PUE) and its isolated active principle, the 4-nerolidylcatechol (4-NC), in bone marrow cells of mice using the micronucleus test. Swiss male mice were orally treated for 4 days with PUE (200, 100 or 50mg/kg/day) or 4-NC (50, 25 or 12.5mg/kg/day) prior to exposition with a single dose (200mg/kg) of cyclophosphamide (CP), 24h after the end of the treatment. The results demonstrated that the PUE and 4-NC did not have any mutagenic effect on mouse bone marrow cells; quite the opposite, there was a protective effect against genotoxicity induced by cyclophosphamide. Taken together, under the conditions tested herein, mice treated with PUE and 4-NC showed, in a dose-dependent manner, protective effect against CP-induced genotoxicity. Due to their ability to prevent chromosomal damage, with apparent low toxicity and cost, PUE or pure 4-NC are likely to open a field of interest concerning their possible use in clinical applications.     

Protective effect of hawthorn extract against genotoxicity induced by cyclophosphamide in mouse bone marrow cells

The preventive effect of hawthorn (Crataegus microphylla) fruit extract was investigated in mouse bone marrow cells against genotoxicity induced by cyclophosphamide. Mice were orally (gavages) pretreated with solutions of hawthorn extract which was prepared at five different doses (25, 50, 100, 200 and 400mg/kg b.w.) for seven consecutive days. Mice were injected intraperitoneally on the seventh day with cyclophosphamide (50mg/kg b.w.) and killed after 24h for the evaluation of micronucleated polychromatic erythrocytes (MnPCEs) and the ratio of PCE/(PCE+NCE) (polychromatic erythrocyte/polychromatic erythrocyte+normochromatic erythrocyte). All of five doses of extract significantly reduced MnPCEs induced by cyclophosphamide (P<0.0001). Hawthorn extract at dose 100mg/kg b.w. reduced MnPCEs 2.5 time and also completely normalized PCE/(PCE+NCE) ratio. Hawthorn extract exhibited concentration-dependent antioxidant activity on 1,1-diphenyl-2-picryl hydrazyl free radical. Hawthorn contains high amounts of phenolic compounds; the HPLC analysis showed that it contained chlorogenic acid, epicatechin and hyperoside. It is obvious that hawthorn, particularly flavonoids constituents with antioxidative activity, reduced the oxidative stress and genotoxicity induced by cyclophosphamide in mouse bone marrow cells.     

度洛西汀对小鼠急性毒性及遗传毒性的研究

目的:探讨度洛西汀对成年雄性小鼠的急性毒性及遗传毒性。方法:采用小鼠急性毒性试验观察致死率及半数致死量(LD₅₀)。采用小鼠骨髓微核试验、小鼠精子畸变试验及生殖与淋巴器官重量指数检测方法,将小鼠均分为6组,即阴性对照组、阳性对照组,度洛西汀1、2、3和4组(分别给予度洛西汀5、10、20和40 mg/kg),观察度洛西汀不同剂量对小鼠精子畸变率、骨髓微核率及生殖与淋巴器官重量指数的影响。结果:度洛西汀急性毒性试验结果表明,灌胃给予度洛西汀的LD₅₀为188.3 mg/kg。微核试验与精子畸变试验结果表明,度洛西汀灌胃剂量为5、10和20 mg/kg时(度洛西汀1、2和3组)均未诱发小鼠精子畸变率和骨髓微核率的改变,与阴性对照组相比,差异均无统计学意义(P>0.05);度洛西汀4组小鼠的精子畸变率、骨髓微核率均高于阴性对照组,差异有统计学意义(P<0.05)。度洛西汀1、2、3和4组小鼠的生殖与淋巴器官重量指数与阴性对照组相比,差异均无统计学意义(P>0.05)。结论:灌胃给予度洛西汀的LD₅₀为188.3 mg/kg,安全性高。度洛西汀以5、10和20 mg/kg的剂量灌胃对小鼠无生殖与遗传毒性,当灌胃剂量达到40 mg/kg时对雄性小鼠有轻微的潜在遗传毒性。     

Lack of in vivo clastogenic activity of grape seed and grape skin extracts in a mouse micronucleus assay.

Meganatural brand grape seed extract (GSE) and grape skin extract (GSKE), containing proanthocyanidin polyphenolic compounds, are intended for use in food as functional ingredients exhibiting antioxidant activity. Proanthocyanidins, as well as the minor constituent phenolic compounds in GSE and GSKE, are present naturally in many foods such as fruits, vegetables, chocolate, tea, etc., and on average people consume 460-1000 mg/day of these combined substances. While some polyphenolic compounds, tested individually, have demonstrated antitumorigenic or antipromotional activity, at least one minor component of GSE and GSKE, quercitin, has exhibited positive activity in Salmonella and other in vitro mutagenicity assays. As part of a program to investigate the safety of GSE and GSKE, these products were tested for in vivo clastogenic activity and/or disruption of the mitotic apparatus by detecting micronuclei in polychromatic erythrocyte (PCE) cells in Crl:CD-1(ICR) BR mouse bone marrow. The appropriate test article was dissolved in 0.5% carboxymethylcellulose and dosed by oral gavage to five males/test article/dose level/harvest time point. Animals were dosed at 500, 1000 and 2000 mg/kg. Five animals dosed with either test article at 500, 1000 and 2000 mg/kg dose levels and five animals dosed with the cyclophosphamide (80 mg/kg) positive control were euthanized approximately 24 h after dosing for extraction of bone marrow. Five animals dosed with either test article at the 2000 mg/kg dose level and five animals dosed with the vehicle control article were euthanized approximately 24 and 48 h after dosing for extraction of bone marrow. At least 2000 PCEs per animal were analyzed for frequency of micronuclei. Cytotoxicity was assessed by scoring the number of PCEs and normochromatic erythrocytes (NCEs) in at least the first 500 erythrocytes for each animal. For both GSE and GSKE, no statistically significant increase in micronucleated PCEs was observed at any dose level or harvest time point. GSE produced indication of cytotoxicity (decreased PCE:NCE ratio) at the 2000 mg/kg dose level for the 48-h harvest time point, confirming that the test article reached the target bone marrow in significant amount. Meganatural GSE and Meganatural GSKE were evaluated as negative in the mouse bone marrow micronucleus assay under the conditions of this assay.     

松针汁的毒性及致突变性研究

对松针汁进行了毒性和致突变性实验。结果显示：松针汁急性毒性试验，ＬＤ５０〉１０ｇ／ｋｇｂｗ；在所示剂量范围内，Ａｍｅｓ试验加与不加Ｓ９活化系统，各剂量组平均回主率均〈２，小鼠骨髓细胞微核试验，各剂量组微核率与阴性对照组比较无明显差异，小鼠精子畸形试验，各剂量组精子畸形率与阴性对照组比较无明业差异，表明松针汁无毒，无致突变作用。     

铊的特殊毒性研究

研究表明,碳酸铊剂量在0.48mg/kg以上能诱发小鼠骨髓细胞做核数增加;浓度为0.047mg/ml时,诱发体外培养细胞形态转化;剂量为0.83～2.5mg/kg的小鼠致畸试验结果,见胚胎吸收率和胸骨及枕骨缺失(或骨化不全)的胎鼠数明显高于对照组,但未见内脏和外观畸形。     

正交设计法研究环磷酰胺诱导小鼠骨髓细胞微核的影响因素

目的　研究环磷酰胺诱导小鼠骨髓细胞微核的影响因素 ,确定其在实验中作为阳性对照剂使用的优化因素水平组合。方法　采用正交设计 ,考察剂量、取样时间、小鼠体重、性别对MN率、PCE/ (PCE +NCE)结果的影响。结果　对MN率 ,上述因素的影响均有统计学意义 (P <0 .0 1 ) ,产生最高MN率的因素水平组合为 :剂量 1 60mg·kg- 1 、取样时间 30h、小鼠体重 1 7～ 1 9g、性别♂。对PCE/ (PCE +NCE) ,仅剂量因素有显著影响 (P <0 .0 1 ) ,当剂量为 1 60mg .kg- 1 时 ,该指标K1 最低 ,为 2 2 .5 % ;其它因素则未显示出明显的影响。结论　根据实验要求 ,经综合考虑二项观察指标结果 ,确定环磷酰胺微核试验的优化因素水平组合条件为 :剂量 80mg·kg- 1 、取样时间ip后 30h、小鼠体重 1 7～ 1 9g、性别♂。     

Role of melatonin in ameliorating lead induced haematotoxicity.

Owing to the risks of heavy metals-induced severe haematopoietic disorders, it is important to investigate these chemicals for their haematotoxicity and the possible ways to ameliorate their toxicity. The effects of melatonin on lead-induced haematotoxicity have, therefore, been examined in rat blood and bone marrow. When adult male rats were injected intramuscularly with lead acetate (10 mg kg(-1)) daily for 7 days, the erthrocytic count, haematocrite value and haemoglobin content were significantly decreased. The counts of platelets, total leucocytes and lymphocytes in the peripheral blood were also significantly lower in lead-treated rats than in control animals. The total granulocyte count was significantly elevated in the peripheral blood of the same lead-treated rats. Significant decreases in polychromatic and pyknotic erythroid series as well as lymphocytes in bone marrow of the lead-intoxicated rats were also demonstrated. Meanwhile, the neutrophiles were increased in the same treated rats. The erythropoietin level was significantly decreased and the lead concentration was increased in the plasma of the lead-treated rats compared with the control rats. Bone marrow examination of the rats treated with lead for 7 days showed erythroid hyperplasia with a sign of dyserythropoiesis and demonstrated ringed sideroblasts in varying proportions. Daily pretreatment with melatonin (30 mg kg(-1)) intragastricaly, concurrently with lead injection for 7 days significantly prevented the changes recorded in the peripheral blood parameters. The changes observed in the bone marrow polychromatic erythroid, lymphocytes and the neutrophiles were significantly ameliorated by coadministration of melatonin and lead compared with lead-treated rats, while the pyknotic erythroid series was still significantly low. The levels of erythropoietin and lead in plasma were not changed in melatonin+lead-treated group compared with lead only treated rats. In addition, melatonin administration ameliorated the decrease in erythroid cell count in bone marrow. Less dyserythropoiesis and megaloblastic changes were observed in bone marrow film when melatonin was concurrently administered with lead. In the same animals, iron staining of the bone marrow cells showed absence of ringed sideroblasts. In conclusion, the present results indicate that melatonin has the ability to protect the haematopoietic cells from the damaging effects of exposure to lead. This protection might be attributed to the antioxidative power of melatonin.