红景天苷注射液遗传毒性的研究

目的：检测红景天苷注射液的遗传毒性。方法：应用微生物回复突变实验（Ames实验,5 000、500、50、5.0、0.5μg/皿）、体外培养CHO细胞染色体畸变实验（2 0001、000、500μg/mL）和小鼠骨髓微核实验法（1 500、750、375μg/kg）检测红景天苷注射液的遗传毒性。结果：红景天苷注射液对鼠伤寒沙门菌无致突变性,对体外培养CHO细胞染色体无致畸变作用,对ICR小鼠无诱发骨髓嗜多染红细胞微核的效应,三个实验结果均呈阴性。结论：红景天苷注射液不具有遗传毒性。     

赤苷脉通注射液对麻醉犬急性心肌缺血的保护作用

目的观察赤苷脉通注射液对犬急性心肌缺血损伤的保护作用。方法采用麻醉犬冠状动脉结扎造成心肌梗死模型,用心外膜标测法测定心肌梗死程度,硝基四氮唑蓝染色法测定心肌梗死面积,并测定血清乳酸脱氢酶（LDH）、肌酸激酶（CK）活性。结果赤苷脉通注射液（4,2,1mg·kg^-1）减轻犬冠脉结扎所致ST段升高总mV数,减小心肌梗死面积,抑制血清LDH、CK活性的升高。结论赤苷脉通注射液对麻醉犬急性心肌缺血损伤有保护作用。     

赤苷脉通注射液对大鼠生育力和早期胚胎发育的毒性研究

目的 研究赤苷脉通注射液(CGMT)对大鼠生育力与早期胚胎发育的毒性.方法 160只SD大鼠随机均分为对照组和CGMT 75、150、300 mg· kg-剂量组;雄鼠交配前9周至交配成功,雌鼠交配前2周至妊娠7d分别连续于尾静脉给药,交配结束处死雄鼠,进行精子数、精子活力和精子形态学等指标检查,孕鼠于妊娠14 d时处死,记录妊娠子宫重量、黄体数和着床数等指标,观察胚胎死亡情况.结果 CGMT各剂量组各项检测指标与对照组相比无显著性差异(P＞0.05).结论 试验条件下,CGMT在300 mg· kg-剂量下对SD大鼠的生育力和早期胚胎发育无明显毒性作用.     

丹参注射液单次给药的毒性及遗传毒性研究

目的研究丹参注射液的单次给药毒性及遗传毒性,为评价其安全性提供毒理学依据。方法采用一次性给予丹参注射液,观察ICR小鼠产生的毒性反应;用体外细菌回复突变(Ames)实验、中国仓鼠肺成纤维细胞(CHL)体外染色体畸变实验、小鼠骨髓嗜多染红细胞微核实验进行丹参注射液的遗传毒性研究。结果在单次给药毒性中,5个剂量组动物死亡数分别为9,7,4,3和0只;Ames实验中,丹参注射液剂量分别为5 000,2 000,500,50和5μg·皿-1,无论加或不加哺乳动物肝脏微粒体酶(S9),各剂量组的回复突变菌落数均未出现剂量依赖性的增加,结果为阴性;在染色体畸变实验中,非活化条件或代谢活化条件下,细胞的染色体畸变率均未出现剂量依赖性增加;在微核实验中,与溶媒对照组比较,丹参注射液各剂量组中的微核率均无显著性差异。结论在本实验条件下,单次给药毒性研究中,丹参注射液小鼠静脉注射给药的LD50为68.72g·kg-1,95%可信限为66.92~70.58g·kg-1,其对小鼠的急性毒性可能靶器官组织为肺脏。遗传毒性实验结果均为阴性,即中药制剂丹参注射液无潜在的致突变性。     

长春西汀的致突变研究

检测长春西汀是否有致突变作用。方法：要用Ａｍｅｓ试验,小鼠微核试验及哺乳动物培养细胞染色体畸变试验观察长春西汀的诱导性。结果：Ａｍｅｓ试验,微核试验及染色体畸变试验结果为阴性,结论：长春西汀在所试条件下未见致突变作用。     

阿比哚致突变作用的研究

目的研究阿比哚的致突变作用。方法应用微生物回复突变试验、小鼠微核试验、哺乳动物培养细胞染色体试验 ,观察阿比哚对细胞的诱变性。结果阿比哚的Ames实验、小鼠体内微核试验、CHL细胞染色体畸变试验均呈阴性结果 ,阿比哚无诱变性。结论阿比哚无致突变作用。     

RP-HPLC法测定脉通胶囊中黄芩苷的含量

目的建立RP-HPLC法测定脉通胶囊中黄芩苷的含量。方法选用Agilent C18色谱柱(5μm,4.6mm×250mm),以甲醇-水-磷酸(40∶60∶0.1)为流动相,流速为1.0mL·min-1,检则波长为280nm。结果黄芩苷线性范围为0.06~3μg。回归方程Y=2791.6X 3.5,r=0.9998,平均加样回收率98.6%,RSD=1.18%(n=5)。结论RP-HPLC法简便,可靠,结果准确,可用于该制剂的质量控制。     

栎精的毒性和致突变作用

栎精是天然植物中提取的一种具有祛痰、止咳，并有一定的平喘作用小分子化合物。做为一种抗氧化剂，可以清除体内有害的化学物质氧自由基，使脑细胞少受氧自由基的损伤；同时研究表明栎精具有明显抗诱变作用。由于其自身结构上具有2个苯环的特点决定了栎精具有明显的抗突变作用又有明显的致突变性。本试验采用Ames试验、小鼠骨髓细胞微核试验和小鼠睾丸精母细胞染色体畸变试验研究栎精的致突变作用。     

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。     

HPLC法测定脑通注射液中芍药苷的含量

目的建立脑通注射液中芍药苷含量测定的HPLC法.方法用Water的C18反相色谱柱(4.6 mm×150mm,5 μm),以甲醇-0.03mol·L-1磷酸二氢钾-5%庚烷磺酸钠(65:30:5)为流动相,流速为1.0 mL·min-1,用二极管阵列检测器检测,检测波长230 nm,柱温30℃.结果方法芍药苷在43.9～219.5μg·mL-1呈良好的线性关系(r=0.999 6),精密度RSD为0.23%(n=7),重现性RSD为1.31%(n=5),芍药苷的平均回收率为99.9%,RSD为0.72%(n=6).结论方法快速、简便,结果准确、可靠,可用于脑通注射液中芍药苷的含量测定.     

Mutagenicity testing of quinine with submammalian and mammalian systems

Quinine hydrochloride was assayed for genotoxic activity by using 4 different test systems with distinct genetic endpoints. No indications for point mutations were observed in the Ames system. In 3 cytogenetic tests performed on small rodents, Chinese hamsters showed no genotoxic activity, while inbred strains of mice revealed a dose dependent increase of SCEs, enhanced incidence of micronuclei and elevated chromatid breaks.     

Developmental toxicity and genotoxicity studies of wogonin

We studied the developmental toxicities and genotoxic potency of a widely bioactive plant medicine-wogonin in vivo and in vitro. In the in vivo developmental experiments, high dose of wogonin (40mg/kg, intravenous injection) significantly induced the maternal weight gains and affected fetus including bodyweight, resorptions, live birth index and fetal skeletal alterations. In Ames test, no concentration-dependently increased TA98, TA100, and TA102 revertants were detected in wogonin groups whether in presence of metabolic activating enzymes or not. In the chromosome aberration test, wogonin dose-dependently increased structural chromosomal aberrations in CHL cells both with and without S9, even the effect was all judged (-). In micronucleus assay, no significant changes of MNPCE/PCE and PCE/NCE were found on mouse bone marrow micronucleus in wogonin groups. We concluded that wogonin induced developmental toxicities on pregnant mice and fetus, and the genotoxicities were positive. However no significant malformation was observed and only in vitro potency of chromosome aberration was weak, which suggested us wogonin could be a relatively safe drug in clinic.     

酸枣仁油的致突变作用的研究

目的对酸枣仁油进行毒理学试验,探讨酸枣仁油是否有致突变作用。方法①小鼠急性毒性试验:一次最大限量法。②Ames试验:选用经鉴定符合要求的鼠伤寒沙门氏组氨酸缺陷型TA97、TA98、TA100、TA102试验菌株,采用平板掺入法。③小鼠骨髓嗜多染红细胞微核试验。结果酸枣仁油对雌雄小鼠经口LD50均>10g/kg,为实际无毒级物质;骨髓嗜多染红细胞微核实验和Ames试验未发现破酸枣仁油对小鼠有致突变作用。结论从毒理学角度可以认为酸枣仁油作为保健食品用于人体是安全的。     

蚓激酶的诱变实验研究

用鼠伤寒沙门氏菌回复突变试验，小鼠骨髓红细胞微核试验及ＣＨＬ细胞染色体畸变试验，对蚓激酶进行了诱变性试验研究。结果表明鼠伤寒沙门氏菌回复突变试验为阴性，该药可能不诱发基因突变；小鼠骨髓红细胞微核试验及ＣＨＬ细胞染色体畸变试验均为阴性，说明该药可能不诱发体内、体外遗传物质损伤作用。     

Podophyllin,but not the constituents quercetin or kaempferol,induced genotoxicity in vitro and in vivo through ROS production

The genotoxic potential of podophyllin (PD) was investigated in this study. PD increased bacterial revertants and abnormal chromosomal structures in a concentration-dependent manner, both with and without metabolic activating enzymes, and increased the incidence of micronuclei in imprinted control region mouse reticulocytes. Results from three studied constituents of PD, such as podophyllotoxin, kampferol, and quercetin, suggested that the mutagenic effect of PD was not due to the presence of podophyllotoxin, kampferol, and quercetin and might be related to other components and the formation of reactive oxygen species. The detailed mutagenic mechanisms need further investigation, and the medicinal use of PD needs to be cautioned against.     

Genotoxicity and antileishmanial activity evaluation of Physalis angulata concentrated ethanolic extract

Antileishmanial in vitro tests, as well as Ames and micronucleus assays were performed with a concentrated ethanolic extract of Physalis angulata (EEPA)ResultsEEPA did not present mutagenic effect in Salmonella typhimurium strains at concentration reaching 3000 μg/plate and did not induce mutagenic effects after two oral administrations with a 24 h interval at a dose level of 2000 mg/kg. EEPA presented antileishmanial activity and presented an IC₅₀ value of 5.35 ± 2.50 μg/mL and 4.50 ± 1.17 μg/mL against Leishmania amazonensis and Leishmania braziliensis promastigotes, respectively. In the cytotoxicity test against macrophages, the EEPA had a LC₅₀ of 6.14 ± 0.59 μg/mL. Importantly, the IC₅₀ against L. amazonensis intracellular amastigotes was 1.23 ± 0.11 μg/mL.ConclusionEEPA extract is non-mutagenic and presented a promising pharmacological effect against Leishmania parasites.     

Mutagenicity and chemopreventive activities of Astronium species assessed by Ames test

In the neotropical savannah, Astronium species are used in popular medicine to treat allergies, inflammation, diarrhea and ulcers. Given that natural products are promising starting points for the discovery of novel potentially therapeutic agents, the aim of the present study was to investigate the mutagenic and antimutagenic activities of hydroalcoholic extracts of Astronium spp. The mutagenicity was determined by the Ames test on Salmonella typhimurium strains TA98, TA97a, TA100 and TA102. The antimutagenicity was tested against the direct-acting and indirect-acting mutagens. The results showed that none of the extracts induce any increase in the number of revertants, demonstrating the absence of mutagenic activity. On the other hand, the results on the antimutagenic potential showed a moderate inhibitory effect against NPD and a strong protective effect against B[a]P and AFB₁. This study highlights the importance of screening species of Astronium for new medicinal compounds. The promising results obtained open up new avenues for further study and provide a better understanding the mechanisms by which these species act in protecting DNA from damage. However, further pharmacological and toxicological investigations of crude extracts of Astronium spp., as well as of its secondary metabolites, are necessary to determine the mechanism(s) of action to guarantee their safer and more effective application to human health.     

抗癌新药——去甲斑蟊素致突变的系列研究

作者近年按国际标准建立了药物短期致突变系列,这一系列包括用于测定基因(点)突变的Ames试验和测定染色体畸变的中国仓鼠肺细胞试验及微核试验。应用这一系列评价了我国创制的抗癌新药——去甲斑蟊素的致突变性.测试系统还将Ames新菌株、CHL-ED_(50)剂量法则、NIH敏感品系小鼠应用于这一系列。实验显示去甲斑蟊素既不诱发基因(点)突变,也不诱发染色体畸变,这是去甲斑蟊素与一般抗肿瘤制剂之不同点.     

Mutagenicity of industrial wastewaters collected from two different stations in northern India

Mutagenicity of wastewaters taken from two different cities was compared by means of Ames plate test and Ames fluctuation test. TA100 and TA98 strains of S. typhimurium exhibited the highest sensitivity against the Saharanpur sample (SWW) in terms of the slope (m) of the dose-response curve in the plate incorporation assay. However, the most sensitive strain against the test samples from Aligarh (AWW) was TA98. Interestingly, TA100 and TA98 strains also displayed the highest susceptibility towards the samples from Saharanpur in the fluctuation test. However, TA102 and TA100 responded maximally to AWW in this bioassay. Interestingly, S9 supplementation resulted in the decline in mutagenic potential of SWW contrary to significant increase with AWW by both the tests. Both samples were found to generate different types of ROS as predominant species. While SWW were shown to generate a high concentration of superoxide radicals and hydrogen peroxide, hydroxyl radicals were predominantly occurring in AWW. From our result, we conclude that both the test water samples were highly genotoxic. In view of the complementary nature of these two testing systems, we recommend both bioassays for the genotoxicity assessment of complex water samples.     

国产RU486的遗传毒理学评价

RU486是一种新型抗孕激素催经止孕药。本文对其进行Ames、染色体畸变及微粒等三项体内外遗传毒性试验。结果Ames及染色体畸变试验无论代谢活化与否,RU486均呈阴性反应;微核试验中,即使RU486用量为1.2g╱kg 24h后(临床用量的400倍)亦不引起小鼠骨髓多染微核率增加。提示RU486无遗传毒性作用。