Evaluation on genotoxicities of raceanisodamine hydrochloride injection / 药学实践杂志

Objective To study the genotoxicities of raceanisodamine hydrochloride injection. Methods Bacterial reverse mutation test, in vitro Chromosomal aberration test and in vivo Micronucleus test were performed to investigate the genotoxicities of raceanisodamine hydrochloride injection. Results The Ames test showed that raceanisodamine hydrochloride injection did not increase mutagenicity for TA1535, TA102, TA100, TA98 and TA97 strains at the dosage of 0.5, 5, 50, 500, 5000 μg per plate under two parallel system conditions (±S9). Results of CA test indicated that there was no statistical difference between raceanisodamine hydrochloride injection groups (doses of 58.75,117.5 and 235.0 μg/ml) and the solvent control group under two parallel system conditions (±S9). In MNT test, with doses of 7.5, 15.0 and 30.0 mg/kg respectively, the micronucleus induction rate of bone marrow of ICR mice was not statistically significant (P>0.05) when compared with that of vehicle control group in all dose groups. Conclusion Under the conditions of these study, the results indicated that raceanisodamine hydrochloride injection had no mutagenicity to Salmonella typhimurium, had no aberration effect on the chromosome of mammalian cultured cells, and had no effect on inducing micronucleus of bone marrow polychromatic erythrocytes in ICR mouse. All test results showed that raceanisodamine hydrochloride injection had no potential carcinogenicities and genetic toxicities under the test conditions.

Effect of passage number on the activity and spontaneous reverse mutation of Ames test strains / 上海预防医学

Objective We explored the stability of the bacteria strains used in the Ames test to provide a basis for determining the appropriate passage number at which the biological characteristics of the strains would not change. Methods The Salmonella typhimurium (TA97a, TA98, TA100 and TA102 strains) were selected as the experimental strains.The original frozen strains and frozen strains with different passage times were used to compare the biological characteristics and the spontaneously reverting colonies. Results The biological characteristics of four kinds of strains, which were histidine deficiency, lipidpolysaccharide barrier defect, ampicillin resistance, UV sensitivity, and tetracycline resistance, did not change at F1-F6 generation when compared with the F0 generation.However, as for the number of spontaneously reverting colonies, a statistically significant difference (P < 0.05) occurred at F3 generation when compared with F0 generation for the TA97a strain, and a significant difference (P < 0.05) occurred at F4 generation for TA100 and TA102 strains. Conclusion Passage number of strains used in Ames test could affect their spontaneous reversion mutation rate.The passage number should be less than 4 for TA98、TA100、TA102 strains, and less than 3 for TA97a in Ames test.

Evaluation of the genotoxicity of ginseng leaf extract UG0712 / 한국실험동물학회지

Although ginseng (genus Panax) leaf extract contains high concentrations of bioactive constituents, its effects have been reported in few preclinical studies, and information regarding its toxicity is not sufficient to allow for its clinical use. We evaluated the genotoxicity of UG0712, which is a powdered extract of ginseng leaves. UG0712 did not increase the number of revertant colonies in 4 histidine auxotrophic strains of Salmonella typhimurium (TA100, TA1535, TA98, and TA1537) or in a tryptophan auxotrophic strain of Escherichia coli (WP2uvrA(pKM101)) at any concentration evaluated, either in the absence or presence of the metabolic activation system. There was no significant increase in the number of metaphase cells with structural or numerical aberrations in the UG0712-treated groups compared to the concurrent vehicle control at any dose, regardless of the presence of the metabolic activation system. Oral administration of the extract at doses up to 2,000 mg/kg in male mice did not increase the frequency of micronucleated polychromatic erythrocytes in the bone marrow, and did not result in any significant clinical signs, body weight loss, gross findings, or mortality. These results suggest that UG0712 does not act as a mutagenic or genotoxic material at the concentrations evaluated.

Appropriate In Vitro Methods for Genotoxicity Testing of Silver Nanoparticles

OBJECTIVES: We investigated the genotoxic effects of 40-59 nm silver nanoparticles (Ag-NPs) by bacterial reverse mutation assay (Ames test), in vitro comet assay and micronucleus (MN) assay. In particular, we directly compared the effect of cytochalasin B (cytoB) and rat liver homogenate (S9 mix) in the formation of MN by Ag-NPs. METHODS: Before testing, we confirmed that Ag-NPs were completely dispersed in the experimental medium by sonication (three times in 1 minute) and filtration (0.2 microm pore size filter), and then we measured their size in a zeta potential analyzer. After that the genotoxicity were measured and especially, S9 mix and with and without cytoB were compared one another in MN assay. RESULTS: Ames test using Salmonella typhimurium TA98, TA100, TA1535 and TA1537 strains revealed that Ag-NPs with or without S9 mix did not display a mutagenic effect. The genotoxicity of Ag-NPs was also evaluated in a mammalian cell system using Chinese hamster ovary cells. The results revealed that Ag-NPs stimulated DNA breakage and MN formation with or without S9 mix in a dose-dependent manner (from 0.01 microg/mL to 10 microg/mL). In particular, MN induction was affected by cytoB. CONCLUSIONS: All of our findings, with the exception of the Ames test results, indicate that Ag-NPs show genotoxic effects in mammalian cell system. In addition, present study suggests the potential error due to use of cytoB in genotoxic test of nanoparticles.

Lack of Mutagenicity Potential of Periploca sepium Bge. in Bacterial Reverse Mutation (Ames) Test, Chromosomal Aberration and Micronucleus Test in Mice

OBJECTIVES: The root barks of Periploca sepium Bge. (P. sepium) has been used in traditional Chinese medicine for healing wounds and treating rheumatoid arthritis. However, toxicity in high-doses was often diagnosed by the presence of many glycosides. The potential mutagenicity of P. sepium was investigated both in vitro and in vivo. METHODS: This was examined by the bacterial reverse mutation (Ames) test using Escherichia coli WP2uvrA and Salmonella typhimurium strains, such as TA98, TA100, TA1535, and TA1537. Chromosomal aberrations were investigated using Chinese hamster lung cells, and the micronucleus test using mice. RESULTS: P. sepium did not induce mutagenicity in the bacterial test or chromosomal aberrations in Chinese hamster lung cells, although metabolic activation and micronucleated polychromatic erythrocytes were seen in the mice bone marrow cells. CONCLUSIONS: Considering these results, it is suggested that P. sepium does not have mutagenic potential under the conditions examined in each study.

Mutagenicity Test for Hot Water Extract of Coix lacryma-jobi L. var. ma-yuen Stapf-Reverse Mutation Test, Mouse Lymphoma Assay (MLA) and Mouse Micronucleus Test / 日本補完代替医療学会誌

<i>Coix lacryma-jobi</i> L. <i>var. ma-yuen</i> Stapf is a grass long been used in traditional medicine as a nourishing food and reported to possess pharmacological effects including anti-tumor, anti-obesity, anti-diabetic, etc. In order to evaluate the possible mutagenicity of the hot water extract of all parts (husks, pellicles, and astringent skin) of the food, we performed a reverse mutation test in bacteria, a mouse lymphoma assay and a mouse micronucleus test. The results of all tests were negative. It was concluded that the extract has no mutagenicity for living bodies.<br>

Cytotoxic, mutagenic and antimutagenic screening of Arenosclera brasiliensis acetone and ethanol extracts

The marine environment is a rich source of biologically active compounds with pharmacological properties. Marine organisms often produce secondary metabolites with structural features different from those produced by terrestrial ones, and the Phylum Porifera seems to be one of the most productive in this sense. This study was undertaken to provide data on mutagenic and antimutagenic activities from an acetone (Areac) and an ethanol (Areet) extract obtained from Arenosclera brasiliensis, an endemic Brazilian sponge. A qualitative Salmonella reverse mutation test was performed with the TA97, TA98, TA100, and TA102 strains by incubating cells with Areac and Areet in the presence and absence of a known mutagen. A cytotoxic evaluation of the extracts was also performed. A. brasiliensis did not display any mutagenic activity, but Areac showed significant toxicity against test strains. In the antimutagenic assay, a reduction in the number of his+ revertants was observed for the TA97, TA100 and TA102 strains treated with Areac when compared to the positive controls. Areet treatment showed protective activity against DNA lesions only for the TA100. These results are in agreement with those obtained previously with other A. brasiliensis extracts, suggesting an antimutagenic activity.

A Novel Screening Method for Isolating High Cholesterol Oxidase Producing Strain / 微生物学通报

The cholesterol oxidase producing strain Brevibacterium sp.DGCDC-82 was treated with NTG (1 mg/mL)under ultrasonicztion(200 W,50 kHz).A red mutant named Brevibacterium sp.DGCCN-25 showed higher and stable production of cholesterol oxidase was obtained.The enzyme activity was increased by 140%,it is 1.24 U/mL.Then dealed with DGCCN-25 using the same method,two revertants were obtained,one was white and the other was rose pink.The enzyme activity of two revertants was obvious decrease,they are 0.17 U/mL and 0.69 U/mL.The results showed the positive correlation between COD acticity and red pigment producing by Brevibacterium sp..The relativity model can be used as a method of screening for mutation and directed evolution.

A STUDY ON THE ANTIMUTAGENESIS EFECCT OF FIVE KINDS OF CHONGQING GREEN TEA / 重庆医科大学学报

This paper reports the antimutagenesis effect of three different preparations of five kinds of Chongqing green tea on four direct and indirect mutagens with Ames test.The results show that acetone extracts and concentrated water extracts of all the above green teas markedly inhibit the mutagenicity of AFB1 and B(a)P.The inhibition rate is above 89%, and the dose-response relation is clear. The inhibition rate of drinking concentration of water extract of the teas for mutagenicity of AFB1 and B(a) P is above 70%. But neither the acetone extracts nor the water extracts of the above green tea inhibit the mutagenicity of the two direct mutagens-2, 7-diaminofluorene and sodium azide, the inhibition rates are all below 20%. The possible mechanisms of action are being discussed