• Title/Summary/Keyword: Reverse mutation

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In vitro Antimutagenic and Genotoxic Effects of Azadirachta indica Extract (님추출물의 in vitro 항돌연변이원성 및 유전독성 영향)

  • Yoon, Hyunjoo;Cho, Hyeon-Jo;Kim, Jin Hyo;Park, Kyung-Hun;Gil, Geun-Hwan;Oh, Jin-Ah;Cho, Namjun;Paik, Min-Kyoung
    • Journal of Applied Biological Chemistry
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    • v.57 no.3
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    • pp.219-225
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    • 2014
  • Azadirachta indica extract (AIE) has been regarded as a promising source of environment-friendly organic materials owing to their low mammalian toxicity. However, quite a bit of research has been reported that AIE may cause clastogens in human lymphocytes. Therefore, this study was conducted to evaluate the antimutagenic and genotoxicity of two samples of AIE. Antimutagenic test was experimented by using bacterial reverse mutation test. In the bacterial reverse mutation test, five strains Salmonella Typhimurim of two samples of AIE in order to evaluate its mutagenic potential. Bacterial reverse mutation test was also performed on positive control and negative control groups in the presence of the metabolic activation system (S-9 mix) and metabolic non-activation system. In the chromosome aberration test, Chinese hamster lung cells were exposed to AIE for 6 or 24 h with BPS, or for 6 h with S-9 mix. Negative and positive control groups were experimented for chromosome aberration test. As a result, the number of mutated colonies induced by 4-NQO were reduced by AIE treatment in all strains, indicating that AIE may have antimutagenic effects. Bacterial reverse mutation and chromosomal aberration were not shown at all concentration of AIE, regardless of activation of the metabolic system. we concluded that two AIE samples used in this study have no genotoxic effects to human, according to the genotoxicity battery system suggested by ICH (International Conference on Harmonization).

In vitro Antimutagenic and Genotoxic Effects of Sophora Radix Extracts (고삼추출물의 in vitro 항돌연변이원성과 유전독성 연구)

  • Cho, Hyeon-Jo;Yoon, Hyunjoo;Park, Kyung-Hun;Lee, Je-Bong;Shim, Chang-Ki;Kim, Jin Hyo;Jeong, Mi Hye;Oh, Jin-Ah;Kim, Doo-Ho;Paik, Min-Kyoung
    • The Korean Journal of Pesticide Science
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    • v.17 no.4
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    • pp.335-342
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    • 2013
  • Sophorae radix extract (SRE) has been registered as an environment-friendly organic material that is widely used in the cultivation of crops in Korea. Matrine, the active ingredient in SRE, was reported as a toxic substance in the nervous system in mice. However, no information is available on its toxic effects in other organisms. Therefore, antimutagenicity and two kinds of genotoxicity tests (bacterial reverse mutation and chromosome aberration test) of two samples of SRE were investigated in this study. Antimutagenicity test was experimented by using bacterial reverse mutation test. In the reverse mutation test, Salmonella Typhimurim TA98, TA1535 and TA1537 were used to evaluate the mutagenic potential of SRE. Bacterial reverse mutation test was also performed on positive and negative control groups in the presence of the metabolic activation system (with S-9 mix) and metabolic non-activation system (without S-9 mix). In the chromosome aberration test, Chinese hamster lung cells were exposed to SRE for 6 or 24 hours without S-9 mix, or for 6 hours with S-9 mix. Negative and positive control groups were experimented for chromosome aberration test. As a result, the number of mutated colonies induced by 4-NQO were reduced by SRE treatment in all strains, indicating that SRE may have antimutagenic effects. Reverse mutation was not shown at all concentrations of SRE, regardless of application of the metabolic activation system. In the chromosomal aberration test, one of the SRE sample gave a suspicious positive result at 250 ${\mu}g/ml$ in the presence of S-9 mix. For the more adequate evaluation of the genotoxic potential of SRE samples, other in vivo genotoxicity study is needed.

Mutagenicity Study of DA-3030, A New Recombinant Human G-CSF(rhG-CSF) (새로운 재조합 인 과립구 콜로니 자극인자 DA-3030의 변이원성연구)

  • 강경구;최성학;김옥진;안병옥;백남기;김계원;김원배;양중익
    • Biomolecules & Therapeutics
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    • v.2 no.3
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    • pp.286-291
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    • 1994
  • The mutagenicity of DA-3030(rhG-CSF)was studied by reverse mutation test, chromosome aberration test and micronucleus test. The reverse mutatuon test in bacteria was performed using salmonella typhimurium strain TA100, TA98, TA1535 and TA1537 with rhG-CSF in any of the concentrations(150, 75, 37.5, 18.75, 9.375 and 4,6875 $\mu\textrm{g}$/plate), no increase in the number of revertant colonies in each strain was observed, irrespective of treatment with the metabolic activation system(S-9 mix) The chromosome aberration test was carried out using CHL cells, cell line from chinese hamster lung. With 4 doses(75, 37.5, 18.75 and 9.375 $\mu\textrm{g}$/ml) of rhG-/CSF the cells were treated for 24 or 48 hours in the direct method or for 6 hours followed by 18 hour-expression time in the metabolic activation method. Results of the study showed, by the direct method or metabolic activation method, no trend toward increase in the number of aberrant metaphase. The micronucleus test was carried out using ICR mice at the age of 8 weeks. Three doses(862.5, 1725 and 3450 $\mu\textrm{g}$/kg) of DA-3030 were admintstered intraperitoneally with single shot and bone marrow cells were sampled at 24 hours after administration. Neither the number of polychromatic erythrocytes with micronuclei nor the ratio of normochromatic erythrocytes to polychromatic erythrocytes increased singinficantly in each dose, compared with a vehicle control. These results indicate that rhG-CSF has not mutagenic potential under the condiions.

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Identification of pol Gene Mutation among BLV Proviruses Found in the Southern Province of Korea

  • Kwon, Oh-Sik
    • The Journal of Korean Society of Virology
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    • v.30 no.2
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    • pp.131-139
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    • 2000
  • Bovine leukemia virus (BLV) is an etiological agent of chronic diseases in cows worldwide. The BLV is one of retroviruses that contain a multi-functional enzyme, reverse transcriptase produced from the pol gene in its genome. We have sequenced some regions in the pol gene of BLV proviruses found in the Southern province of Korea from samples that turned out to be BL V positives by a PCR analysis. On the 5' side of the BLV pol gene (polymerase region), it was found that there were four leucines located at every 7 amino acids. They can form a leucine zipper motif that was not same as the pol gene of Japanese BLV isolate. The sequencing result of the proviral pol gene in Korean-type BLV also revealed some mutations leading to amino acid changes such as $CCT(Pro){\to}CTC(Leu)$, $AAT(Asn){\to}AAA(Lys)$, and non-sensible variations i.e., $TCT(Ser){\to}TCC(Ser)$, $ATT(Ile){\to}ATC(I1e)$ and $ACG(Thr){\to}ACA(Thr)$. On the 3' side of the pol gene (integrase region), some nucleotide sequences were mutated and led to amino acid changes. Among them, a mutation, $GAA(Glu){\to}GAC(Asp)$ occurred in many Korean-type BLV proviruses was very interesting because the amino acid was regarded as one of the most conserved amino acids in the retroviral integrase. It was also notable that the mutation on any leucine residue did not occur, in spite of its frequent appearance.

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Mutagenicity Study of Purified Bee Venom (Apis mellifera L.) by the Bacterial Reverse Mutation Assay (세균을 이용한 정제봉독의 복귀돌연변이시험)

  • Han, Sang Mi;Hong, In Phyo;Woo, Soon Ok;Kim, Se Gun;Jang, Hye Ri
    • Journal of Food Hygiene and Safety
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    • v.32 no.3
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    • pp.228-233
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    • 2017
  • The aim of the current study was to examine genotoxicological safety of purified bee venom (Apis mellifera L.) The bacterial reverse mutation in Salmonella typhimurium (TA100, TA1535, TA98, and TA1537) and Escherichia coli (WP2 uvrA) were evaluated with purified bee venom at concentrations of 0, 1.5, 5, 15, 50, 150, and $500{\mu}g/plate$. Purified bee venom was negative in Ames test with both in the presence and absence of rat liver microsomal enzyme. According to these results, we concluded that purified bee venom did not cause bacterial reverse mutation. The safety of the purified bee venom at practical doses needs to be further evaluated in in vivo genotoxicity assays.

Safety Evaluation of Korean Mistletoe Extract (한국산 겨우살이 추출물의 안전성 평가)

  • Kim, Inbo;Jeong, Ju-Seong;Yoon, Taek Joon;Kim, Jong Bae
    • The Korean Journal of Food And Nutrition
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    • v.26 no.3
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    • pp.383-390
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    • 2013
  • Mistlero C was shown to be non-genotoxic in a series of genotoxicity tests, including a bacterial reverse mutation test and a combined in vivo mammalian erythrocyte micronucleus test. In a bacterial reverse mutation assay, no significant increases in the number of revertant colonies, compared to the negative control, was detected in $5,000{\mu}g/plate$ of Mistlero C. In addition, with Mistlero C, no changes were shown in the number of micronucleated polychromatic erythrocytes (MNPCE) among 2,000 polychromatic erythrocytes compared to the negative control. Mistlero C was administered orally in rats to investigate acute toxicity. The $LD_{50}$ values in rats were above 2,000 mg/kg. In a repeated dose, 13-week, oral toxicity study conducted in rats, no compound-related adverse effects were shown at doses of Mistlero C of up to 1,000 mg/kg body weight/day. The results of these studies support the safe use of Mistlero C in food for human consumption.

Genotoxicity Study of Litsea japonica Fruit Flesh Extract (까마귀쪽나무열매추출물의 유전독성 평가)

  • Yun, Ji-Hyun;Park, In-Jae;Park, Sung-Hwan;Choi, Goo-Hee;Kim, Hyun-Jung;Cho, Ju-Hyun
    • Journal of Food Hygiene and Safety
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    • v.33 no.3
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    • pp.207-213
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    • 2018
  • This study aimed to evaluate the genotoxicity of Litsea japonica fruit-hexane extract (LJF-HE). In order to examine the genotoxicity, we carried out bacterial reverse mutation assay, chromosome aberration assay, and a micronucleus induction (MN) test according to the OECD and the Korea Ministry of Food and Drug Safety (MFDS) toxicity test guidelines. In the bacterial reverse mutation assay, no significant increase in revertant colonies, nor bacterial toxicity, was observed in the LJF-HE treatment group, regardless of the absence or presence of metabolic activation by the S9 mixture. However, in the positive control group, revertant colony counts were shown to be more than twice that of the negative control group. The chromosome aberration test showed that the repetition rate of abnormal chromosome aberration was less than 5%, regardless of the treatment time, and with or without the S9 mixture. No significant change was observed when (p < 0.05) compared with the negative control group. The micronucleated polychromatic erythrocytes (MNPCE) repetition rate of the polychromatic erythrocytes (PCE) showed no significant changes when compared with the negative control group (p < 0.05). The PCE portion of total erythrocytes also showed no significant changes (p < 0.05). These results showed that LJF-HE had no significant genotoxic effects.

Genotoxicity Study of Immature Green Persimmon Extract (풋감 주정 추출물의 유전독성 연구)

  • Ham, Young-Min;Yoon, Seon-A;Hyun, Ho Bong;Go, Boram;Jung, Yong-Hwan;Oh, Dae-Ju;Yoon, Weon-Jong
    • Journal of Food Hygiene and Safety
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    • v.35 no.6
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    • pp.567-573
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    • 2020
  • The persimmon is commonly cultivated in temperate regions of the world, including China, Korea, Japan, Brazil, Turkey, and Italy. In some Asian cultures, consumers are aware of the health claims related to the persimmon and its functional ingredients. The rich phytochemistry of the persimmon has opened new avenues of research on diet-based regimens designed to cure various ailments. This study was conducted to identify the genotoxicity of immature green persimmon (Diospyros kaki THUNB.) extract (DKA). The bacterial reverse mutation assay, the chromosomal aberration assay, and the mammalian micronucleus test were performed to determine the DKA genotoxicity. The result of the bacterial reverse mutation assay revealed that the DKA did not induce mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2uvrA with or without metabolic activation of S9 mixture. The oral administration of DKA also caused no significant increase in the number of micronucleated polychromatic erythrocytes or in the mean ratio of polychromatic to total erythrocytes. In addition, DKA did not cause a significant chromosome aberration on CHL cells in the presence or absence of S9 activation. In conclusion, DKA could be considered as a reliable and safe functional food since no toxicity was found under the condition of this study.

Development of Anti-viral Agents from Natural Sources

  • Hattori, Masao
    • Plant Resources
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    • v.4 no.3
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    • pp.192-195
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    • 2001
  • Human immunodeficiency virus (HIV), the causative agent of AIDS, still continues to spread rapidly in the world population, especially in Africa and Southeast Asia. At present, two kinds of therapeutic approaches are used for treatment of AIDS. One is to target HIV reverse transcriptase, which is responsible for the viral genome transcription. The other is to inhibit HIV pretense PR, which is essential for the processing of viral proteins. Drug combinations based on these approaches can reduce the blood virus to an undetectable level. However, a small amount of virus may lurk inside the immune cells in a dormant state. Another major obstacle of long-term treatment of the disease is remarkable mutation in HIV. Most of the clinical chemotherapeutic agents have one or more of these problems. High cost and harmful side-effects further reduced the desirability of these drugs. In the course our studies on development of anti-HIV agents from natural products, we investigated various crude drugs for their inhibitory activity against HIV-induced cytopathic effects (CPE) in culture cells, HIV-pretense (PR), HIV-reverse transcriptase (RT) including ribonuclease H (RNase H), and HIV integrase (INT). In the present paper, some inhibitory substances relating to the development of anti-HIV agents are reported.

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