Absence of genotoxicity of potato alkaloids alpha-chaconine, alpha-solanine and solanidine in the Ames Salmonella and adult and foetal erythrocyte micronucleus assays.

To assess whether reported toxicities of potato-derived glycoalkaloids could be the result of interactions with cellular DNA, the genotoxic effects of alpha-solanine, alpha-chaconine and solanidine were studied, using the Ames test (Salmonella strains TA98 and TA100), the mouse peripheral blood micronucleus test and the mouse transplacental micronucleus test. The Ames test for mutagenicity with alpha-solanine was weakly positive in TA100 with S-9 activation (29 revertants per millimole per plate). However, pooled data from duplicate tests gave a negative effect. Pooled data from two experiments with alpha-chaconine gave a weak positive response in TA98 without microsomes (17 revertants per millimole per plate). The micronucleus tests for clastogenicity using male mouse and foetal blood were negative. The absence of mutagenicity and clastogenicity suggests lack of damage to intracellular DNA for potato alkaloid toxicity.     

赤苷脉通注射液的致突变研究

目的探讨中药制剂赤苷脉通注射液的致突变性。方法采用鼠伤寒沙门氏组氨酸营养缺陷型菌株回复突变实验(Ames实验)、中国仓鼠肺成纤维细胞(CHL)染色体畸变实验和小鼠骨髓微核实验来检测赤苷脉通注射液的致突变作用。结果 Ames实验中,赤苷脉通注射液在312.5～5 000μg.皿-1剂量范围内,无论加或不加S9,鼠伤寒沙门氏菌组氨酸缺陷型TA97,TA98,TA100,TA102和TA1535 5株菌的回复突变菌落数均未出现剂量依赖性的增加;染色体畸变实验中,非活化条件或代谢活化条件下,药物质量浓度为1 200,600和300μg.mL-1时,细胞的染色体畸变率均未出现剂量依赖性增加;微核实验中,在1 150,575和287.5mg.kg-1剂量组中均未见骨髓中含微核的嗜多染红细胞数增加。结论在该实验室条件下,Ames实验、CHL细胞染色体畸变实验和小鼠骨髓微核实验结果均为阴性,即中药制剂赤苷脉通注射液无潜在的遗传毒性。     

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。     

聚乙二醇修饰降纤酶的遗传毒性评价

目的检测聚乙二醇修饰降纤酶的遗传毒性。方法应用鼠伤寒沙门菌回复突变试验(Ames试验)、体外培养CHO细胞染色体畸变试验和小鼠骨髓微核试验检测聚乙二醇修饰降纤酶的遗传毒性。结果 Ames试验结果显示每平皿100、20、4、0.8、0.16 U各个剂量组,在加或不加S9代谢活化系统时对组氨酸缺陷型鼠伤寒沙门菌TA97、TA98、TA100、TA102及TA1535所诱发的回复突变菌落数均与溶剂对照的突变菌落数相近。体外培养CHO细胞染色体畸变试验结果显示2.5、5.0和10.0 U.mL-1各个剂量组在加S9代谢活化系统于24 h和不加S9代谢活化系统于24 h、48 h培养的CHO细胞染色体畸变率与溶剂对照组比较均无显著差异(P>0.05)。小鼠骨髓微核试验显示425、850、1700 U.kg-1各个剂量组对ICR小鼠的微核诱发率与溶剂对照组比较均无显著差异(P>0.05)。结论聚乙二醇修饰降纤酶对鼠伤寒沙门菌无致突变性,对哺乳动物培养细胞的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。表明聚乙二醇修饰降纤酶在本实验条件下无遗传毒性。     

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。     

Acute, subacute toxicity and genotoxic effect of Bio-Quinone Q10 in mice and rats

In the present study, the acute, subacute and genetic toxicity of Coenzyme Q10 (CoQ10) in the form of Bio-Quinone (Pharma Nord, Denmark) was assessed. LD(50) of CoQ10 by oral treatment was greater than 20g/kg body weight in both female and male mice. Genotoxicity was assessed in mice by Ames test in Salmonella typhimurium strains TA97, TA98, TA100 and TA102, by bone marrow micronucleus test and sperm abnormality. Thirty-day subacute toxicity was conducted with oral daily dose at 0, 0.56, 1.13 and 2.25g/kg body weight in rats. No significant changes in body weight, food intake, behavior, mortality, hematology, blood biochemistry, vital organ weight, sperm abnormality, mutagenicity and micronucleus formation were observed and no clinical signs or adverse effects were detected by administration of CoQ10. These results support the safety of CoQ10 for oral consumption.     

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.     

中药复方藿莲香Ⅰ号的遗传毒理学研究

目的：根据前期藿莲香Ⅰ号药效学研究结果,进一步研究该复方的急性毒性和致突变作用,为其进一步应用的安全性提供理论依据。方法应用急性毒性实验、小鼠骨髓嗜多染红细胞微核试验、小鼠骨髓细胞染色体畸变试验和Ames试验检测该组分配伍复方的急性毒性和致突变性。结果急性经口毒性试验：雌性、雄性小鼠经口MTD均大于10g＆#183;kg-1,属实际无毒。致突变实验：小鼠骨髓嗜多染红细胞微核试验、小鼠骨髓细胞染色体畸变试验和Ames试验结果均为阴性,显示在本实验条件下,该中药复方未见有致突变性作用。结论中药复方藿莲香Ⅰ号未见有明显的急性毒性和致突变作用,表明该药物安全性良好。     

Study of mutagenicities of phthalic acid and terephthalic acid using in vitro and in vivo genotoxicity tests

Genotoxicities of phthalic acid (PA) and terephthalic acid (TPA) were examined using three mutagenicity tests: Ames, chromosome aberration (CA), and micronucleus (MN). In the Ames test, these two agents did not produce any mutagenic responses in the absence or presence of S9 mix on the Salmonella typhimurium strains TA98, TA100, TA102, TA1535, or TA1537. The CA test also showed that PA and TPA exerted no significant cytogenetic effect on Chinese hamster ovary (CHO) cells. In the mouse MN test, no significant alteration in occurrence of micronucleated polychromatic erythrocytes was observed in ICR male mice ip administered any of these agents at doses of 0, 20, 100, 500, 2500 or 12,500 microM/kg. These results indicate that PA and TPA produced no mutagenic effects using these in vitro and in vivo mutagenic test systems.     

Effects of vitamin A on cyclophosphamide mutagenicity in vitro (Ames test) and in vivo (mouse micronucleus test)

The effect of vitamin A on cyclophosphamide mutagenicity was measured both in vitro and in vivo. In the Ames test in Salmonella typhimurium TA 1535 with mouse-liver S-9 mix, the addition of retinol, retinyl acetate or retinyl palmitate caused a dose-dependent inhibition of cyclophosphamide mutagenicity. In the micronucleus test in male NMRI mice fed low, normal or high levels of vitamin A, the induction of micronuclei in bone marrow by an ip dose of cyclophosphamide was unaffected by vitamin A status. Thus, this study provides no evidence that activation of a procarcinogen in the liver or bone marrow of mice can be modified by vitamin A. One of the possible reasons for the observed absence of inhibition by vitamin A in vivo may be a lack of correlation between the oral dose of retinoid and the resulting level of vitamin A in the bone marrow. The difference between results in vitro and in vivo may also have been due to a difference in the availability and potency of added vitamin A in vitro compared with the forms absorbed and stored in vivo.     

Genotoxic evaluation of Halfenprox using the human peripheral lymphocyte micronucleus assay and the Ames test

The genotoxicity and mutagenicity of Halfenprox, a synthetic pyrethroid insecticide and acaricide, was assessed using two standard genotoxicity assays of the Salmonella typhimurium mutagenicity assay (Ames test) and in vitro micronucleus (MN) assay in human peripheral lymphocytes. In the Ames test, Salmonella strains TA98 and TA100 were treated with or without S9 fraction. The doses of Halfenprox were 6.25, 12.5, 25, 50, and 100?μg/plate and test materials were dissolved in DMSO. The concentrations of Halfenprox did not show mutagenic activity on both strains with and without S9 fraction. The MN assay was used to investigate the genotoxic effects of Halfenprox in human peripheral lymphocytes treated with 250, 500, 750, and 1000?μg/ml concentrations of Halfenprox for 24 and 48?h, and at 1000?μg/ml the concentration was significantly increased and the MN formation was compared with the negative control for both treatment periods. In addition, a significant decrease of the nuclear devision index (NDI) values at the higher concentrations of Halfenprox and at both treatment periods was observed.     

二乙基二硫代氨基甲酸钠抑制顺铂的致突变作用

二乙基二硫代氨基甲酸钠（ＤＤＴＣ）能明显抑制顺铂诱导鼠伤寒沙门氏菌ＴＡ１００，ＴＡ９８回变，有Ｓ９代谢活化系统时抑制作用增强，１６０．７４μｇ／ｐｌａｔｅＤＤＴＣ对０．２５～２．００μｇ／ｐｌａｔｅ顺铂抑制率为８７．４％～９５．７％（ＴＡ１００）和８９．４％～１０５．５％（ＴＡ９８）．小鼠ｉｐ顺铂１．５ｍｇ·ｋｇ－１，２４ｈ重复ｉｐ１次，每次给顺铂后１ｈｉｐＤＤＴＣ４００～８００ｍｇ·ｋｇ－１或同时ｉｇＤＤＴＣ７５０～１５００ｍｇ·ｋｇ－１．可显著降低顺铂诱发小鼠骨髓多染红细胞微核的形成．体内外实验结果表明ＤＤＴＣ可降低顺铂的致突变作用     

Disposition of [14C]2,3-dichloropropene in Fischer-344 rats after oral or intraperitoneal administration

The genotoxicity of indigo has been assessed by two short-term tests. The mutagenicity of natural indigo was compared with that of synthetic indigo. Both chemicals were tested using the standard procedure of the Salmonella/microsome mutagenicity test as described by Ames. The substance exhibits mutagenicity towards strains TA1538 and TA98 when S9 preparations of rat liver induced with Aroclor 1254 were present in the medium. The clastogenic potential was evaluated by the micronucleus test in the bone marrow of male mice. The test compound was administered twice with an interval of 24 h, the animals were killed 30 h and 54 h after the first treatment. When the test compound was given by oral gavage as two equal dosages of 0.1, 1 and 1.2 g/kg body weight, no statistically significant increase in the percentage of polychromatic erythrocytes with micronuclei was observed for any group treated with natural indigo.     

中药浮海石致突变的实验研究

目的研究中药浮海石致突变性。方法本试验采用鼠伤寒沙门菌回复突变试验(Ames试验),哺乳动物培养细胞(CHL)染色体畸变试验和小鼠骨髓细胞微核试验观察了浮海石的致突变作用。结果浮海石生理盐水浸提液0.5~5000μg/皿剂量下Ames试验结果阴性;250~1000μg/mL剂量下对CHL细胞无损伤作用,10~40g/kg剂量下对小鼠骨髓细胞染色体无致畸变作用。结论浮海石无致突变作用,用于临床是安全的。     

Absence of mutagenicity of acid pyrogallol-containing hair gels.

In the present work, three commercial acid (pH 3.5-4) pyrogallol-containing hair gels, SunSet Alizador Negro (two formulations) and Embelleze Henê Gel, were tested for mutagenicity using two well-established assays. In the Salmonella mutagenicity assay using 648-5000 microg/plate of cosmetic samples, none of the samples reached a 2-fold increase in revertants relative to the controls. Both in the absence and in the presence of S9, the dose-response relation in strains TA98, TA100, TA102, TA1535, and TA1537 was not significant (p>0.01). In the mouse bone marrow micronucleus assay, 10 Swiss male mice were orally administered 2000 mg/kg of sample per body weight/day. The ratio between polychromatic and normochromatic erythrocytes as well as the presence of micronuclei in bone marrow cells were determined. Equal numbers of micronucleated polychromatic erythrocytes were detected between the cells of each treated group and the negative control, using ANOVA and chi-square analyses. Thus, none of the products induced mutagenesis in either assay. Previous studies have shown pyrogallol is mutagenic in various test systems, including Salmonella. However studies have also shown that acidic conditions may repress the reactive-oxygen species (ROS) produced by pyrogallol, and ROS is considered the primary mechanism for the mutagenicity of pyrogallol. Consistent with this are our results, which show that acidic, commercially available pyrogallol-containing hair gels are neither mutagenic in Salmonella nor induce micronuclei in mouse bone marrow in vivo.     

白障明的诱变性试验研究

作者用鼠伤寒沙门氏菌回变试验,小鼠骨髓红细胞微核试验及CHL细胞染色体畸变试验,对白障明进行了诱变性试验研究。结果表明鼠伤寒沙门氏菌回变试验为阴性,该药可能不诱发基因突变,NIH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,体外染色体损伤作用。     

Non-clastogenicity in mouse bone marrow of fructose/lysine and other sugar/amino acid browning products with in vitro genotoxicity

Heated sugar/amino acid reaction mixtures, known to contain products that are clastogenic and/or mutagenic to cells in vitro, were evaluated for clastogenic activity in mouse bone marrow using the erythrocyte micronucleus assay. Heated (i.e. browned) fructose/lysine reaction mixtures were also evaluated in the Salmonella his-reversion assay and the Chinese hamster ovary (CHO) cell chromosomal aberration assay to confirm and extend previous in vitro observations. Significant mutagenicity of fructose/lysine mixtures was observed in Salmonella typhimurium strains TA100, TA2637, TA98 and TA102, with greater activity in mixtures heated at pH 10 than at pH 7. S-9 decreased the activity in strains TA100, TA2637 and TA98, but increased the activity in strain TA102. Both pH 7 and pH 10 reaction mixtures of the fructose/lysine browning reaction were highly clastogenic in CHO cells. Heated mixtures of fructose and lysine, and of glucose or ribose with lysine, histidine, tryptophan or cysteine, did not increase the frequency of micronucleated erythrocytes in mice when administered by the oral route. This indicates the absence of chromosomal aberrations in erythrocyte precursor cells, and indicates that the genotoxic components of the browned mixtures are not absorbed and distributed to bone marrow cells in amounts sufficient to induce micronuclei when given orally. Because sugar/amino acid browning reactions occur commonly in heated foods, it is important to evaluate further the in vivo genotoxicity of browning products in cell populations other than bone marrow.     

Tinospora cordifolia, a safety evaluation

Tinospora cordifolia is one of the indispensable medicinal plants used in veterinary folk medicine/Ayurvedic system of medicine for the treatment of diverse diseases and recommended for improving the immune system by means of body resistance. In the current study, we evaluated the genotoxic risk of the aqueous extract of T. cordifolia (TC) in a battery of four different genotoxicity tests viz., Ames, in vitro chromosome aberration (CA), rodent bone marrow micronucleus (MN), and Comet assay. Experimental results confirmed that in Ames test up to 5000 μg/plate of TC did not exhibit any mutagenic effect in Salmonella typhimurium mutant strains (TA97a, TA98, TA100, TA102, and TA1535). In CA assay, TC was not clastogenic to human peripheral blood lymphocytes up to a concentration of 3000 μg/ml. In MN and Comet assays, TC was pre-treated for 7 days at three dose levels (150, 200 and 250 mg/kg body weight) orally to male Balb/c mice. The results showed that TC treatment did not display clastogenicity and DNA damaging effect in bone marrow erythrocytes and peripheral blood lymphocytes respectively.     

苦荞降糖胶囊的致突变性研究

目的研究苦荞降糖胶囊的致突变性。方法分别采用Ames试验、小鼠骨髓嗜多染红细胞微核试验和小鼠精子畸形试验对基因水平和细胞水平的遗传损伤进行检测。结果该胶囊在0.1、0.5、1.0、2.0和5.0mg/皿的剂量下对TA97、TA98、TA100和TA102四株试验菌株均未引起自发回变菌落数增加;在1250和5000mg/kg体重剂量下均未引起小鼠骨髓嗜多染红细胞微核率和小鼠精子畸形率升高(字2检验,P>0.05)。结论该胶囊在基因水平和细胞水平均不具有致突变性。     

Mutagenic and antimutagenic assessment of methanol leaf extract of Myristica fragrans (Houtt.) using in vitro and in vivo genetic assays

The role of diets in causing cancers necessitates the ongoing search for natural antimutagens of promising anticancer therapeutics. This study determined the potential anticancer efficacy of the leaf extract of Myristica fragrans (Houtt.). Methanol leaf extract of M. fragrans (Houtt.) alone was screened for mutagenicity in the bacterial reverse mutation (Ames) test, using the Salmonella typhimurium TA100 strain, the Allium cepa, and the mouse in vivo bone marrow micronucleus tests. The antimutagenicity of this extract against benzo[a]pyrene- and cyclophosphamide-induced mutations was evaluated. An antioxidant test on the extract was performed with 2,2-diphenyl-1-picrylhydrazyl, using butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) as the standards, whereas its phytochemicals were elucidated by following the gas chromatography/mass spectrometry protocol. In S. typhimurium (TA100), the mutagenicity ratio at 200,500 and 1,000 μg/well was >2. Cell division in the A. cepa root tips and mouse bone marrow was significantly (P?≤?0.05) inhibited at 2,000 and 4,000?mg/kg, whereas the observed chromosomal aberrations and micronucleated polychromatic erythrocytes were non-dose-related and were insignificantly (P?≥?0.05) different from the negative control. Inhibition of benzo[a]pyrene- and cyclophosphamide-induced mutagenicity by this extract was above 40%. Half-maximal inhibitory concentration of the extract in the antioxidant test was lower than that of BHA and BHT. Phytochemical compounds, possessing antioxidant activity, may be responsible for the observed effects, suggesting a strong antimutagenic activity of the MeOH leaf extract of M. fragrans, a necessary characteristic of a promising anticancer agent.