• Toxicological Research
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• 제18권4호
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• pp.385-391
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• 2002

The genotoxic potential of Hyrubicin lD6105, a novel anthracycline anticancer agent, was examined on bacterial mutagenicity, mammalian cell chromosome aberration and mouse micronucleus tests. In mutagenicity (Ames') test, Salmonella typhimurium strain TA98, TA100, TA1535 and TA1537, and Escherichia coli WP2uvrA- were treated with ID6105 at doses of 312.5, 625, 1,250, 2,500 and 5,000 $\mu\textrm{g}$/ plate with or without a metabolic activation system (S9 mix). Interestingly, ID6105 significantly enhanced the number of revertant colonies of TA98 strain at all dose levels used, in the presence or absence of S9 mix, without affecting other strains of S. typhimurium and E. coli. In chromosome aberration test using cultured chinese hamster lung fibroblasts, ID6105 (1.25, 2.5 and 5 $\mu\textrm{g}$/ml) did not increase the number of aberrant cells, compared with vehicle control. in the presence or absence of S9 mix. In addition, ID6105 treatment (2.5, 5 and 10 mg/kg) did not induce micronucleated polychromatic erythrocytes in mice. Taken together, it is suggested that ID6105 might not affect chromosome integrity in mammalian system in vitro and in vivo, although it may induce frame shift mutation of specific bacterial strain such os S. typhimurium TA98.

• 방사선산업학회지
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• 제9권4호
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• pp.181-185
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• 2015

Today the biosafety evaluation, a common problem of vital importance, is based on internationally proved test-systems, standards and techniques. The paradigm of biosafety includes multidisciplinary approach, a combination of physical, chemical and biological tests to monitor the environmental level of pollutants and needs to be improved by modern approaches. The genetic risk of environmental pollutions has long been studied by many researchers. In this study, used was the known sensitive plant test-system, clones of plant Tradescantia (spiderwort) able to detect gene mutations (frequency of mutational events and formation of micronuclei) in combination with chemical and, in some instances, with radiological measurements. In addition, male gametophyte generation of fruit trees was applied as bioindicators of genotoxicity. The obtained results did not show any significant increase along with wind direction. As for the male gametophyte assay, the fertility of the investigated fruit-trees near to NPP did not significantly differ from that of the control point. The influence of the NPP on the male generative system of the investigated taxa of fruit trees for the investigated year was not revealed. The system described needs to be expanded by species of interest (human) as there is a difficulty to transfer the revealed dose correlations to humans. The development of this idea includes various levels: population (epidemiological studies), individual, cellular, molecular (DNA), etc.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2003년도 추계학술대회
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• pp.121-121
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• 2003

• 한국식품영양과학회지
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• 제46권9호
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• pp.1045-1052
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• 2017

본 연구에서는 고메이신 함유 옥수수수염 추출물의 유전독성에 대한 안전성을 규명하고자 세균에서의 복귀돌연변이 유발성, 염색체 이상, 마우스 골수세포에 있어서 소핵실험을 수행하였다. 세균에서의 복귀돌연변이 유발성 여부는 Salmonella Typhimurium의 히스티딘 요구성 균주인 TA100, TA1535, TA98 및 TA1537의 4개 균주와 대장균 Escherichia coli의 트립토판 요구성 균주인 WP2 uvrA를 이용하여 대사활성계 적용(+S9 Mix) 및 비적용(-S9 Mix)하에서 유전 손상을 측정한 결과 모든 균주에서 대사활성계 적용 및 비적용 시 옥수수수염 추출물(5,000, 1,666.67, 555.56, 185.19, $61.73{\mu}g/plate$)에서 복귀돌연변이 평균 집락수의 변화 및 농도 의존적인 증가는 관찰되지 않았다. 염색체 이상 실험에서 대사활성계 적용 및 비적용 6시간 처리군(최고농도 $1,250{\mu}g/mL$)과 대사활성계 비적용 24시간 처리군(최고농도 $250{\mu}g/mL$)에서 이상 중기상 발현 빈도의 증가 및 음성대조군에 비하여 통계적으로 유의성이 확인되지 않았다. 마우스 골수세포에서의 소핵실험에서는 모든 투여용량의 옥수수수염 추출물(0, 500, 1,000, 2,000 mg/kg)에서 다염성 적혈구 중 소핵다염성 적혈구의 출현 빈도 및 총 적혈구에 대한 다염성 적혈구의 출현 빈도가 음성대조군과 비교하여 유의한 차이가 없었으므로 2,000 mg/kg 옥수수수염 추출물의 섭취는 마우스 골수세포의 소핵 유도에 영향을 주지 않는 것으로 판단된다. 결론적으로 세균에서의 복귀돌연변이 실험, 염색체 이상 실험 및 생체 내에서의 마우스 골수세포에서의 소핵시험을 통하여 본 실험 조건에서 고메이신 함유 옥수수수염 추출물은 유전독성을 유발하지 않는 것을 확인하였다.

• 동의생리병리학회지
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• 제23권5호
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• pp.1145-1153
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• 2009

The object of this study was to obtain acute information single oral dose toxicity of Mahwangbujaseshin-tang extracts, with mouse bone marrow cell micronucleus test for detecting possible genotoxicity. In order to observe the 50% lethal dose, approximate lethal dosage, maximum tolerance dosage and target organs, test articles were once orally administered to ICR mice at dose levels of 2000, 1000, 50 mg/kg according to the recommendation of KFDA Guidelines. The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after dosing according to KFDA Guidelines with organ weights of 12 types of principle organs. In addition, after twice oral treatment of Mahwangbujaseshin-tang extracts 2000, 1000 and 500 mg/kg, we checked the changes on the number of MNPCE. We could not find any mortality, clinical signs, changes in the body weight and gross findings upto 2000 mg/kg treated group. The limited dosages in rodents except for increases of lymphoid organ weights and hypertrophy encounted as results from pharmacological effects of Mahwangbujaseshin-tang extracts, immune modulator effects with some sporadic accidental findings not toxicological signs. No evidence of increases of MNPCE numbers were also detected in all three different dosages of Mahwangbujaseshin-tang extracts treated mice. The results obtained in this study suggest that the LD50 and ALD of Mahwangbujaseshin-tang extracts in mice were considered as over 2000 mg/kg because no mortalities were detected upto 2000 mg/kg that was the highest dose recommended by KFDA and OECD. And the results of mouse bone marrow micronucleus test of Mahwangbujaseshin-tang extracts is negative results.

• Molecular & Cellular Toxicology
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• 제3권1호
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• pp.53-59
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• 2007

This study was conducted to evaluate the mutagenic potential of dimethyl isophthalate (DMIP) using Ames bacterial reverse mutation test, chromosomal aberration test and mouse lymphoma $tk^{+/-}$ gene assay. As results, in Ames bacterial reversion assay, DMIP was tested up to the concentration of 5,000 ${\mu}g$/plate and did not induce mutagenicity in Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537, and Escherichia coli WP2uvrA with or without metabolic activation (S9 mix). Using cytotoxicity test, the maximal doses of DMIP for chromosomal aberration assay were determined at 1,250 ${\mu}g/mL$, which was a minimum precipitation concentration ($IC_{50}>1,940\;{\mu}g/mL$ or 10 mM) and at 155 ${\mu}g/mL$ ($IC_{50}:155\;{\mu}g/mL$) in the presence and the absence, respectively, of S9 mix. DMIP in the presence of S9 mix induced statistically significant (P<0.001) increases in the number of cells with chromosome aberrations at the dose levels of over 250 ${\mu}g/mL$, when compared with the negative control. However, DMIP in the absence of S9 mix did not caused significant induction in chromosomal aberrant cells. In MLA, DMIP at the dose range of 242.5-1,940 ${\mu}g/mL$ in the presence of S9 mix induced statistically significant increases in mutation frequencies related to small colony growth, whereas any significant mutation frequency was not observed in absence of S9 mix. From these results, it is conclusively suggested that dimethyl isophthalate may be a clastogen rather than a point mutagen.

• Toxicological Research
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• 제24권2호
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• pp.151-159
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• 2008

Rhus verniciflua Stokes(RVS), one of traditional medicinal plants in Asia, was found to have pharmacological activities such as antioxidative and antiapoptotic effects, raising the possibility for the development of a novel class of anti-cancer drugs. Thus, potential genotoxic effects of RVS in three short-term mutagenicity assays were investigated, which included the Ames assay, in vitro Chromosomal aberration test, and the in vivo Micronucleus assay. In Ames test, the addition of RVS water extracts at doses from 313 up to 5000 mg/plate induced an increase more than 2-fold over vehicle control in the number of revertant colonies in TA98 and TA1537 strains for detecting the frame-shift mutagens. The similar increase in reversion frequency was observed after the addition of RVS ethanol extracts. To assess clastogenic effect, in vitro chromosomal aberration test and in vivo micronucleus assay were performed using Chinese hamster lung cells and male ICR mice, respectively. Both water and ethanol extracts from RVS induced significant increases in the number of metaphases with structural aberrations mostly at concentrations showing the cell survival less than 60% as assessed by in vitro CA test. Also, there was a weak but statistically significant increase in number of micronucleated polychromatic erythrocytes(MNPCEs) in mice treated with water extract at 2000 mg/kg while ethanol extracts of RVS at doses of up to 2000 mg/kg did not induce any statistically significant changes in the incidence of MNPCEs. Therefore, our results lead to conclusion that RVS acts as a genotoxic material based on the available in vitro and in vivo results.

• 대한한의학회지
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• 제32권1호
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• pp.67-83
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• 2011

Objectives: The purpose of this study was to examine the single dose toxicity with oral administration and genotoxicities of Ssanghwa-tang fermented with Lactobacillus acidophyllus. Materials and Methods: Clinical signs, weight changes, lethal doses$(LD_{50})$, and postmortem evaluation were determined by Globally Harmonized Classification System(GHCS) in a single-dose oral toxicity study. In vitro mammalian chromosomal aberration test was conducted with Ames test by cell proliferation suppression assessment using the cultivated CHO-K1(Chinese hamster ovary fibroblast) origins. Bacterial reversion assay was performed using Salmonella typhimurium (TA98, TA100, TA1535, and TA1537) and Escherichia coli (WP2uvrA). In vivo micronucleus test was performed using ICR mouse bone marrow. Results: No clinical sign was observed and none of the groups with doses up to 2000 mg/kg showed significant acute oral toxicity in the single dose oral administration. None of the sample doses taken during the 6 to 18 hour groups showed significant aberrant metaphases comparing to the negative control group in the in vitro mammalian chromosomal aberration test. No evidence of mutagenicity was seen for Escherichia coli (WP2uvrA) or Salmonella typhimurium (TA98, TA100, TA1535, and TA1537). No significant increase in the frequency of micronuclei was seen in the micronucleus test. Conclusion: These results indicate that the $LD_{50}$ value of Ssanghwa-Tang fermented with Lactobacillus acidophyllus may be over 2000 mg/kg and it have no acute oral toxicity and genotoxicity.

• 동의생리병리학회지
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• 제24권1호
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• pp.124-133
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• 2010

The object of this study was to obtain acute information single oral dose toxicity of Mahwangbujaseshin-tang extracts, with mouse bone marrow cell micronucleus test for detecting possible genotoxicity. In order to observe the 50% lethal dose, approximate lethal dosage, maximum tolerance dosage and target organs, test articles were once orally administered to ICR mice at dose levels of 2000, 1000, 50 mg/kg according to the recommendation of KFDA Guidelines. The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after dosing according to KFDA Guidelines with organ weights of 12 types of principle organs. In addition, after twice oral treatment of Mahwangbujaseshin-tang extracts 2000, 1000 and 500 mg/kg, we checked the changes on the number of MNPCE. We could not find any mortality, clinical signs, changes in the body weight and gross findings upto 2000 mg/kg treated group. The limited dosages in rodents except for increases of lymphoid organ weights and hypertrophy encounted as results from pharmacological effects of Mahwangbujaseshin-tang extracts, immune modulator effects with some sporadic accidental findings not toxicological signs. No evidence of increases of MNPCE numbers were also detected in all three different dosages of Mahwangbujaseshin-tang extracts treated mice. The results obtained in this study suggest that the LD50 and ALD of Mahwangbujaseshin-tang extracts in mice were considered as over 2000 mg/kg because no mortalities were detected upto 2000 mg/kg that was the highest dose recommended by KFDA and OECD. And the results of mouse bone marrow micronucleus test of Mahwangbujaseshin-tang extracts is negative results.

• 한국연초학회지
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• 제13권1호
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• pp.19-26
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• 1991

Ames test using special strains which are histidine requiring mutant of Salmonella typhimufium , is widely utilized as short-term bioassay to evaluate the genotoxicity of chemicals. This method requires the liver microsome(5-9 fraction) to provide mammalian metabolism of the compounds, Therefore, the mutagenic potency of the chemicals is affected by not only the intrinsic properties of them but also the efficiency of the in vitro microsomal activation system. For this reason, the complex mixtures such as environmental pollutants from occupational sources, natural products or cigarette smoke condensates(CSC) , might be often appeared the false results. Induction of sister chromatid exchange(SCE) in cultured cells is known as another sensitive and powerful tool for the measurement of genotoxicity and the method has also an advantage which is able to apply to the in vitro and in vivo systems. In the present study, the inducibilities of revertant colonies in tester strain TA98 and SCE in human Iymphocytes by positive controls and total particulated materials(TPM) obtained from various brand(domastic and imported) cigarettes were compared in order to investigate whether the results in Ames test are in agreement with those in SCE analysis. The mutagenic activities of well known mutagens such as B(a)P showed excellent dose-response in the both methods although the induction mechanism was different each other, but cyclophosphamide resulted such effect only in SCE analysis. Most TPM tested showed a similar pattern in the mutagenic activities in those methods. However, only two(one imported brand and one domestic sample cigarettes) among the TMP obtained from various cigarettes appeared the higher induction in SCE than Ames test.