• Journal of Ginseng Research
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• 제43권4호
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• pp.562-571
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• 2019

Background: Ginsenosides have been widely used clinically for many years and were regarded as very safe. However, a few researches on the toxicities of these kinds of agents showed that some ginsenosides may have side-effect on the rats or dogs. So it is extremely necessary to further clarify the potential toxicity of ginsenosides. This study was carried out to investigate long-term toxicity and genotoxicity of 25-methoxydammarane-3, 12, 20-triol ($25-OCH_3-PPD$), a new derivative of ginsenoside, in beagle dogs. Methods: Twenty-four beagle dogs were divided randomly into four treatment groups and repeatedly orally administered with $25-OCH_3-PPD$ capsule at 60, 120, and 240 mg/kg/day for 91 consecutive days. Ames, micronucleus, and chromosomal aberration tests were established to analyze the possible genotoxicity of $25-OCH_3-PPD$. Results: There was no $25-OCH_3-PPD$einduced systemic toxicity in beagle dogs at any doses. The level of $25-OCH_3-PPD$ at which no adverse effects were observed was found to be 240 mg/kg/day. The result of Ames test showed that there was no significant increase in the number of revertant colonies of $25-OCH_3-PPD$ administrated groups compared to the vehicle control group. There were also no significant differences between $25-OCH_3-PPD$ administrated groups at all dose levels and negative group in the micronucleus test and chromosomal aberration assay. Conclusion: The highest dose level of $25-OCH_3-PPD$ at which no adverse effects were observed was found to be 240 mg/kg per day, and it is not a genotoxic agent either in somatic cells or germs cells. $25-OCH_3-PPD$ is an extremely safe candidate compound for antitumor treatment.

• 한국식품영양과학회지
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• 제30권6호
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• pp.1137.2-1245
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• 2001

생약재의 기능성 식품 및 대체의약 원료로의 이용증대에 따라 위생적 저장.유통을 위한 감마선조사 기술의 이용 가능성을 검토할 목적의 일환으로 실제 이용선량의 최고선량 인 10 kGy의 감마선 조사 생약재 3종의 유전독성학적 안전성을 평가하고자 하였다. 공시 재료는 감마선 조사된 생약재료 감초, 진피 및 시호로 하였다. 시험은 Salmonella typhimurium 균주를 이용한 유전자 복귀돌연변이 시험(Ames test)과 배양된 Chinese hamster ovary(CHO) 세포를 이용한 in vitro 소핵유발 시험으로 시행하였다. 시료는 오염유기체 완전 구제 선량인 10 kGy의 감마선으로 조사된 감초, 진피 및 시호의 열수 추출물이었으며, 시료의 농도는 복귀돌연변이 시험의 경우 5 mg/plate로, 소핵유발 시험의 경우 50%의 세포증식 억제를 나타내는 농도를 최고 농도로 하였다. 시험은 대사 활성화시키지 않은 경우와 S9 mix 첨가로 대사 활성화시킨 경우로 나누어 시행하였다. 복귀돌연변이 시험 결과 각 시료에 의한 복귀변이 집락수의 증가를 인정할 수 없었으며, 각 용량단계에서 감마선 비조사군과 조사군간의 차이도 볼 수 없었으므로 음성으로 판정하였다. 소핵유발 시험에서 cytokinesis-blocked binucleated(CB) cells 내에 생성된 소핵을 계수한 결과, 음성 대조군의 경우 소핵 출현빈도가 20~30/1,000 CB cells(2~3%) 정도였으며, 비조사 시료군과 감마선 조사 시료군의 각 용량단계에서 모두 2~4%의 소핵 출현빈도를 보여 시료에 의한 소핵 출현빈도의 증가를 인정할 수 없었다. 따라서 감마선이 조사된 각 시료가 직접변이원이나 간접변이원으로 작용하지 않으며, 세포분열 중에 유전학적으로 독성을 나타내지 않음을 확인할 수 있었다. 이 결과로 보아 생체내 유전독성시험, 만성독성시험 및 생식독성시험 등이 추가된다면 감마선 조사 생약재의 안전성을 명확히 밝힐 수 있을 것으로 사료된다

• 한국식품위생안전성학회지
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• 제16권2호
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• pp.145-151
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• 2001

유아 식품중의 병마개 등에 약 30%까지 함유되어 합성수지 및 고무의 가소제로 많이 사용되고 있으나 최근 유럽등지에서 식품으로의 유리가 보고되어 안전성에 대한 재평가가 요구되어지고 있는 에폭시화 대두유 (Epoxidized soy bean oil, ESBO)의 유전독성을 평가하기 위해서 박테리아를 이용한 복귀돌연변이시험과 포유류 배양세포를 대상으로 검색하는 체외 염색체이상시험, 설치류의 조혈세포를 이용한 체내 소핵시험을 수행하였다. Salmonella typhimurium TA98, TA100, TA1535, TA1537, TA102균주를 이용한 복귀돌연변이 시험결과 직접법 및 대사활성화법에서 돌연변이 유발성을 가지지 않는 음성의 결과를 나타내었으며, chinese hamster lung cell을 이용한 염색체이상시험을 실시한 결과, 직접법 및 대사활성화법에서 염색체이상 유발작용을 보이지 않는 음성의 결과를 나타내었다. 또한 성별, 연령별에 따라서 마우스 골수세포를 이용한 소핵시험에서 에폭시화 대두유는 미성숙 적혈구중 유의성 있는 소핵 유발은 관찰되지 않았다. 이상의 결과를 종합하여, 본 시험조건 중 에폭시화 대두유는 in vitro 시험인 Salmonella 균주를 이용한 복귀돌연변이시험과 포유동물 배양세포를 이용한 염색체이상시험 및 in vivo 시험인 마우스를 이용한 소핵시험에서 유전독성을 유발하지 않는 것으로 판단된다.

• Biomolecules & Therapeutics
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• 제3권4호
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• pp.294-300
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• 1995

DA-3002, an authentic recombinant human growth hormone(rhGH), was examined for mutagenicity in the reverse mutation test on bacteria, in the chromosomal aberration test on cultured mammalian cells and in the micronucleous test on mice. The reverse mutation test was performed by a plate incorporation method with or without a metabolic activation system(S9 Mix) using Salmonella typhimurium strain TA100, TA1535, TA98 and TA1537. DA-3002 did not significantly increase revertant colonies in any of the test strains under any conditions at dose levels ranging from 0.0125 to 0.4 IU/plate, compared with the vehicle control. In the chromosomal aberration test using cultured Chinese hamster lung(CHL) cells, DA-3002 did not increase the number of aberrant cells in the presence or absence of S9 mix at concentrations of 0.0125 IU/mι to 0.4 IU/mι, compared with the vehicle control. In the micronucleus test, male ICR mice were given DA-3002 intraperitoneally at a dose level of 20, 40 and 80 lU/kg. The incidence of bone marrow micronucleated polychromatic erythrocytes in the DA-3002 treated mice did not differ from that of the vehicle control. These results indicate that DA-3002 doesn't have mutagenic potential under the present test conditions.

• Archives of Pharmacal Research
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• 제12권2호
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• pp.94-98
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• 1989

Induction of micronuclei by diesel emission particle extract (DEPE) in mouse bone marrow cells was suppressed by pre-treatment with ascorbic acid, ${\alpha}-tocopherol$ or glutathione (GSH). These compounds were given orally to mice at the dose of 1, 10 or 100 mg/kg/day for 5 consecutive days. The dose of DEPE (200 mg/kg) was administered intraperitoneally once to mice with the 5th administration of test compounds. Ascorbic acid, ${\alpha}-tocopherol$ and GSH all showed the dose-dependent suppression on DEPE-induced micronuclei.

• 한국환경성돌연변이발암원학회지
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• 제18권2호
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• pp.89-92
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• 1998

The results of chromosome aberration test in mammalian cells in culture (Chinese hamster lung fibroblast cells) showed no induction of structural and numerical aberrations by YH1226, a cephalosporin antibiotic regardless of metabolic activation, while positive control group (mitomycin C and benzo(a)pyrene) showed structural chromosome aberrations of 25% and 10%, respectively. The in vivo induction of micronuclei was measured in polychromatic erythrocytes in bone marrow of male ddY mouse given YH1226 at 500, 250, 125 mg/kg by i.p. once. After 24 hours, animals were sacrificed and evaluated for the incidence of micronucleated polychromatic erythrocytes in whole erythrocytes. Although a positive response for induction of micronuclei in animals treated with mitomycin C demonstrated the sensitivity of the test system for detection of a chemical clastogen, YH1226 did not induce microunclei in bone marrow of ddY male mice.

• 한국환경성돌연변이발암원학회지
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• 제21권1호
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• pp.44-50
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• 2001

To identify nongenotoxic carcinogen determined as negative by ICH guideline-recommended standard genotoxicity test battery; Ames test, chromosome aberration assay, mouse lymphoma $tk^{+/-}$ assay, in vivo micronucleus assay, we picked bisphenol A as a model compound. In this study, we applied in vitro BalB/c 3T3 cell transformation assay and Syrian hamster embryo (SHE) cell transfarmation assay. Bisphenol A was treated upto $769.2 ug/m{\ell}$ in BalB/c 3T3 cells and upto $125 ug/m{\ell}$ in SHE cells. bisphenol A didn't induced morphological transformation both with one stage treatment protocol and with two stage treatment protocol. But, treated far 48 hr, Bisphenol A induced morphological transformation significantly in SHE cells.

• 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.

• Molecular & Cellular Toxicology
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• 제3권2호
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• pp.107-112
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• 2007

o-Nitrotoluene is used to synthesize artificial dyes and raw materials of urethane resin. In this study, we have carried out in vitro genetic toxicity tests and microarray analysis to understand the underlying mechanisms and the mode of action of toxicity of onitrotoluene. TA1535 and TA98 cells were treated with o-nitrotoluene to test its toxicity by basic genetic toxicity test. Ames and two new in vitro micronucleus and COMET assays were applied using CHO cells and L5178Y cells, respectively. In addition, microarray analysis of differentially expressed genes in L5178Y cells in response to o-nitrotoluene was analyzed using Affymatrix genechip. The result of Ames test was that o-nitrotoluene treatment did not increase the mutations both in base substitution strain TA1535 and in frame shift TA98. o-Nitrotoluene has not increased micronuclei in CHO cells. But onitrotoluene increased DNA damage in L5178Y cell. Two-hundred two genes were initially selected as differentially expressed genes in response to o-nitrotoluene by microarray analysis and forty four genes among them were over 2 times of log fold changed. These forty four genes could be candidate biomarkers of genetic toxic action of o-nitrotoluene related to induction of mutation and/or induction of micronuclei and DNA damage. Further confirmation of these candidate markers related to the DNA damage will be useful to understand the detailed mechanism of action of o-nitrotoluene.

• Molecular & Cellular Toxicology
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• 제3권2호
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• pp.90-97
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• 2007

8-Hydroxyquinoline is used as antibacterial agent and antioxidant based on its function inducing the chelation of ferrous ion present in host resulting in production of chelated complex. This complex being transported to cell membrane of bacteria and fungi exerts antibacterial and antifungal action. In this study, we have carried out in vitro genetic toxicity tests and microarray analysis to understand the underlying mechanisms and the mode of action of toxicity of 8-hydroxyquinoline. TA1535 and TA98 cells were treated with 8-hydroxyquinoline to test its toxicity by basic genetic toxicity test, Ames and two new in vitro micronucleus and COMET assays were applied using CHO cells and L5178Y cells, respectively. In addition, microarray analysis of differentially expressed genes in L5178Y cells in response to 8-hydroxyquinoline were analyzed using Affymatrix genechip. The result of Ames test was that 8-hydroxyquinoline treatment increased the mutations in base substitution strain TA1535 and likewise, 8-hydroxyquinoline also increased mutations in frame shift TA98. 8-Hydroxyquinoline increased micronuclei in CHO cells and DNA damage in L5178Y. 8-Hdroxyquinoline resulted in positive response in all three tests showing its ability to induce not only mutation but also DNA damage. 783 Genes were initially selected as differentially expressed genes in response to 8-hydroxyquinoline by microarray analysis and 34 genes among them were over 4 times of log fold changed. These 34 genes could be candidate biomarkers of genetic toxic action of 8-hydroxyquinoline related to induction of mutation and/or induction of micronuclei and DNA damage. Further confirmation of these candidate markers related to their biological function will be useful to understand the detailed mode of action of 8-hydroxyquinoline.