• Title/Summary/Keyword: Mutagenic activity

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변이원성 Heterocyclic Amine에 대한 Maillard 반응생성물의 변이원성 억제효과 (Desmutagenic Effects of Maillard Reaction Products against Mutagenic Heterocyclic Amines)

  • 김선봉;박영호;조뢰문효;가등박통
    • 한국수산과학회지
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    • 제19권2호
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    • pp.127-135
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    • 1986
  • D-glucose-glycine계로 부터 조제한 Maillard 반응생성물을 한외여과로 각 분자량별로 분획(분자량 1,000이하, $1,000{\sim}5,000$, 5,000이상)하고, 투석에 의하여 비투석성 melanoidin을, 오존처리에 의하여 오존처리 melanoidin을 각각 얻었다. 이들 각 시료를 아미노산 및 단백질의 가열분해 유래의 변이원성 물질인 TrP-P-1, TrP-P-2, Glu-P-1, Glu-P-2 및 IQ에 각각 작용($37^{\circ}C$, 30분) 시켜서, 변이원성억제효과를 검토하였다. 그 결과, Maillard반응생성물의 변이원성억제효과는 반응생성물의 분자량의 크기에 비례하여 높게 나타났다. Maillard 반응생성물의 환원력 및 항산화력 또한 분자량이 큰 획분일수록 크게 나타났다. 그러나, Sodium borohydride로 melanoidin을 환원시켰을 때, melanoidin의 변이원성억제효과 및 환원력이 감소하였다. 또한, Trp-P-1의 일부가 melanoidin 분자중에 흡착되는 것이 밝혀졌고, 카르 보닐화합물(diacetyl 및 glyceraldehyde)로 이들 변이원성물질의 아미노기를 수식함으로써 변이원성물질의 변이원활성이 크게 저하하였다. 따라서, Maillard 반응생성물 즉 melanoidin의 변이원성억제효과는 melanoidin의 환원력 및 항산화능을 비롯하여 정전기적인 흡착 및 melanoidin 분자중의 카르보닐기에 기인한다고 추찰된다.

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닥나무 부산물에 대한 문헌 연구 (Analysis of studies on the by-products of the Broussonetia kazinoki Siebold or Broussonetia papyrifera (L.) Vent.)

  • 이남헌;하혜경;이호영;정다영;최지윤;최영재;정승일;신현규
    • 한국한의학연구원논문집
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    • 제14권1호
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    • pp.49-58
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    • 2008
  • Objective : To provide information about the accessory product of Broussonetia kazinoki Siebold or Broussonetia papyrifera (L.) Vent by analyzing old books of oriental medicine, domestic/international papers and related patents Methods : Old books related to the accessory product in the field of oriental medicine were reviewed. Research papers regarding the pharmacological activity of the by-products were reviewed and analyzed. Patents about the residual products were examined and classified by year and subject Results : Seven kinds of by-products from Broussonetia kazinoki Siebold or Broussonetia papyrifera (L.) Vent has been used as medicines in oriental medicine. Recently, anti-oxidating, anti-cancer, anti-mutagenic and anti-inflammation activity of the residual product of these plants has been investigated through scientific research. There were 19 patents related with the accessory products of these plants, which were in the subjects of functional cosmetics, anti-inflammation, cleansing goods, hair restorers or improvement of learning ability. Further investigations about the activity of these plants are needed in bone metabolism, water balance and hemostasis in the future. Conclusion : Residual products from these plants is being used in various ways. However, more studies on the efficacy and mechanism, as well as safety, of these plants should be conducted precisely in the future.

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N-methyl-N-nitro-N'-nitrosoguanidine의 변이원성에 대한 빈랑 물 추출물의 돌연변이 억제효과 (Desmutagenic Effect of Water Extract from Areca catechu L. on the Mutagenicity of N-Methyl-N-Nitro-N'-Nitrosoguanidinein in E. coli PQ37)

  • 오위걸;안병용
    • 한국약용작물학회지
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    • 제20권1호
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    • pp.16-19
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    • 2012
  • The desmutagenic activity of the water extract of Areca catechu L. on the mutagenicity induced by aflatoxin $B_1$ ($AFB_1$), N-methyl-N-nitro-N'-nitrosoguani-dine (MNNG), mitomycin C (MMC) and 4-nitroquinoline 1-oxide (4-NQO) was studied by using the SOS Chromotest with Escherichia coli PQ37. The inhibition rates of water extract of Areca catechu L. at concentration of $100{\mu}g/assay$ were 41.0%, 47%, 46%, and 32% against $AFB_1$, MNNG, MMC and 4-NQO, respectively. The water extract of Areca catechu L. was separated into methanol soluble and methanol insoluble parts. The methanol insoluble part exhibited higher inhibition effect than the methanol soluble part against the mutagenic activities of MNNG. Step-wise fractionation of methanol insoluble part was done to obtain methanol, ethyl acetate and water fractions. Among these fractions, water fraction had the strongest inhibitory effect of 45.0% against mutagenicities of MNNG. The inhibition rates of aqueous fraction of methanol-insoluble from water extracted Areca catechu L. at concentrations of 1.61, 16.13, 161.29 and $322.58{\mu}g/mL$ were 12.0%, 24.0%, 47.5% and 62.0%, respectively. The water fraction showed the inhibitory effects with dose response against the mutagenic activity induced by MNNG.

Galactose epimerase결손 Salmonella pullorum 변이주의 효소활성 (Characterization of enzymatic activity of galactose epimerase-less mutant of Salmonella pullorum)

  • 김종배
    • 대한수의학회지
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    • 제34권4호
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    • pp.781-785
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    • 1994
  • Uridine diphosphate(UDP)-galactose-4-epimerase-less mutants of Salmonella pullorum were isolated after mutagenic treatment with ethidium bromide. When isolated gal E mutants of S. pullorum A2 and D1 were grown in the presence of galactose(0.1 W/V), they exhibited marked bacteriolysis in heart infusion broth. The mutant strains were further investigated the characteristics of enzymatic activities in the Leoloir galactose pathway. Isolated A2 and D1 strains were completely deficient in UDP-galactose-4-epimerase activity. And the activity of other enzymes involved in galactose metabolism were reduced significantly.

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Benzo[a]pyrene의 변이원성에대한 인진쑥 물 추출물의 항돌연변이 효과 (Desmutagenic Effect of Water Extract from Artemisia capillaris THUNB on the Mutagenicity of Benzo[a]pyrene)

  • 안병용
    • KSBB Journal
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    • 제15권4호
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    • pp.331-336
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    • 2000
  • 여름과 가을에 수확한 연진쑥을 열수 빛 에탄올로 추출하 여 B(a)P의 변이원성에 대한 억제효과를 SOS Chromotest로 시험한 결과 여름에 수확한 시료의 물 추출물에서 강한 억제 효과를 나타내었다. 따라서 에탄올 가용성 분획과 불용성 분 획으로 분리하였으며 분획별 돌연변이 억제효과는 불용성 분 획에서 더 높게 나타났다. 불용성 분획은 SOS Chromotest외 A Ames test에서 정확한 용량의존성 억제효과를 나타내었고, 50% 돌연변이 억제농도 $(IC_{50}$는 E. coli PQ37에 대하여는 $200{\mu}g/assay$, S. typhimurium TA98에 대하여는 $800{\mu}b/plate$ TAIOO에서는 $600{\mu}g/plate$이었다. 그러나 세포내.외 항돌연변이 효과를 비교한 결과 세포내 항돌연변이 효과는 나타내지 않았다 따라서 인진쑥 물 추출물의 돌연변이 억제효과는 d desmutagenic effect에 의한 것으로 확인되었다 HPLC를 사용 하여, B(a)P의 변이원성에 주된 효소인 cytochrome P-4S0 1A1에 의해 대사되어지는 aflatoxin Mj 농도를 측정한 결 과 AFM1의 형성이 크게 감소되었다. B(a)P의 변이원성에 대 한 인진쑥 불추출물의 항돌연변이 효과는 아마도 B(a)P를 ultimate mutagen으로 대사시키는 cytochrome P-4S0 1A1 효소계를 저해하여 나타나는 것으로 해석된다.

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Genotoxicity on Structural Derivatives of Sophoricoside, a Component of Sophora Japonica, in Bacterial and Mammalian Cells

  • Ryu, Jae-Chun;Kim, Youn-Jung;Kim, Mi-Soon;Kim, Min-Ji;Sarma, Sailendra Nath;Jung, Sang-Hun
    • Molecular & Cellular Toxicology
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    • 제1권3호
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    • pp.179-188
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    • 2005
  • To develop the novel anti-allergic drug, many sophoricoside derivatives were synthesized. Among these derivatives, JSH-II-3, VI-3, VII-3, VIII-3, VII-20 and VII-20 (sodium salt) were selected and subjected to high throughput toxicity screening (HTTS) because they revealed strong IL-5 inhibitory activity and limitation of quantity. Single cell gel electrophoresis (Comet) assay, mouse lymphoma thymidine kinase ($tk^{+/-}$) gene assay (MOLY), chromosomal aberration assay in mammalian cells and Ames reverse mutation assay in bacterial system were used as simplified, inexpensive, short-term in vitro screening tests in our laboratory. Through the primary screening using the comet assay, we could choose the first candidates of sophoricoside derivatives with no genotoxic potentials as JSH-VI-3, VII-3, VII-20 and VII-20 (sodium salt). Also JSH-VII-3, VII-20 and VII-20 (sodium salt) are non-mutagenic in MOLY assay, while JSH-II-3 is mutagenic at high concentration with the presence of metabolic activation system in both comet assay and MOLY assay. The selected derivatives (JSH-VI-3, VII-3, VII-20 and VII-20 (sodium salt) are not mutagenic in S. typhimurium TA98 and TA100 strains both in the presence and absence of metabolic activation. From results of chromosomal aberration assay, 6 h treatment of JSH-VI-3, VII-3 and VII-20 (sodium salt) were not revealed clastogenicity both in the presence and absence of S-9 mixture. Therefore, we suggests that JSH-VI-3, VII-3, VII-20 and VII-20 (sodium salt), as the optimal candidates with both no genotoxic potential and IL-5 inhibitory effects must be chosen. To process the development into new anti-inflammatory drug of these derivatives, further investigation will need.

Development of Fecal Microbial Enzyme Mix for Mutagenicity Assay of Natural Products

  • Yeo, Hee-Kyung;Hyun, Yang-Jin;Jang, Se-Eun;Han, Myung-Joo;Lee, Yong-Sup;Kim, Dong-Hyun
    • Journal of Microbiology and Biotechnology
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    • 제22권6호
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    • pp.838-848
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    • 2012
  • Orally administered herbal glycosides are metabolized to their hydrophobic compounds by intestinal microflora in the intestine of animals and human, not liver enzymes, and absorbed from the intestine to the blood. Of these metabolites, some, such as quercetin and kaempherol, are mutagenic. The fecal bacterial enzyme fraction (fecalase) of human or animals has been used for measuring the mutagenicity of dietary glycosides. However, the fecalase activity between individuals is significantly different and its preparation is laborious and odious. Therefore, we developed a fecal microbial enzyme mix (FM) usable in the Ames test to remediate the fluctuated reaction system activating natural glycosides to mutagens. We selected, cultured, and mixed 4 bacteria highly producing glycosidase activities based on a cell-free extract of feces (fecalase) from 100 healthy Korean volunteers. When the mutagenicities of rutin and methanol extract of the flos of Sophora japonica L. (SFME), of which the major constituent is rutin, towards Salmonella typhimurium strains TA 98, 100, 102, 1,535, and 1,537 were tested using FM and/or S9 mix, these agents were potently mutagenic. These mutagenicities using FM were not significantly different compared with those using Korean fecalase. SFME and rutin were potently mutagenic in the test when these were treated with fecalase or FM in the presence of S9 mix, followed by those treated with S9 mix alone and those with fecalase or FM. Freeze-dried FM was more stable in storage than fecalase. Based on these findings, FM could be usable instead of human fecalase in the Ames test.

Correlation-based and feature-driven mutation signature analyses to identify genetic features associated with DNA mutagenic processes in cancer genomes

  • Jeong, Hye Young;Yoo, Jinseon;Kim, Hyunwoo;Kim, Tae-Min
    • Genomics & Informatics
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    • 제19권4호
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    • pp.40.1-40.11
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    • 2021
  • Mutation signatures represent unique sequence footprints of somatic mutations resulting from specific DNA mutagenic and repair processes. However, their causal associations and the potential utility for genome research remain largely unknown. In this study, we performed PanCancer-scale correlative analyses to identify the genomic features associated with tumor mutation burdens (TMB) and individual mutation signatures. We observed that TMB was correlated with tumor purity, ploidy, and the level of aneuploidy, as well as with the expression of cell proliferation-related genes representing genomic covariates in evaluating TMB. Correlative analyses of mutation signature levels with genes belonging to specific DNA damage-repair processes revealed that deficiencies of NHEJ1 and ALKBH3 may contribute to mutations in the settings of APOBEC cytidine deaminase activation and DNA mismatch repair deficiency, respectively. We further employed a strategy to identify feature-driven, de novo mutation signatures and demonstrated that mutation signatures can be reconstructed using known causal features. Using the strategy, we further identified tumor hypoxia-related mutation signatures similar to the APOBEC-related mutation signatures, suggesting that APOBEC activity mediates hypoxia-related mutational consequences in cancer genomes. Our study advances the mechanistic insights into the TMB and signature-based DNA mutagenic and repair processes in cancer genomes. We also propose that feature-driven mutation signature analysis can further extend the categories of cancer-relevant mutation signatures and their causal relationships.

Salmonella/microsomal enzyme activation system에서의 농약의 돌연변이 유발성 (Mutagenicity of pesticides in the Salminella/Microsome System)

  • 변우현
    • 미생물학회지
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    • 제14권3호
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    • pp.128-128
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    • 1976
  • 19 pesticides including 12 insecticides, 2 herbicides and 5 fungicides have been tested for mutagenic activity in the Salmonella/microsome system. It was found that insecticides, DDVP, Trichlorfon, Sumithion, Naled, fungicide, TMTD and herbicide NIP induced base substitute mutation and herbicide MO frameshift mutation. Mutagenicity of Sumithion and NIP was appeared only after rat microsomal enzyme activation and that of TMTD was increased after the microsomal enzyme activation.

Salmonella/microsomal enzyme activation system에서의 농약의 돌연변이 유발성 (Mutagenicity of pesticides in the Salminella/Microsome System)

  • 변우현;현형환;이세영
    • 미생물학회지
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    • 제14권3호
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    • pp.123-134
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    • 1976
  • 19 pesticides including 12 insecticides, 2 herbicides and 5 fungicides have been tested for mutagenic activity in the Salmonella/microsome system. It was found that insecticides, DDVP, Trichlorfon, Sumithion, Naled, fungicide, TMTD and herbicide NIP induced base substitute mutation and herbicide MO frameshift mutation. Mutagenicity of Sumithion and NIP was appeared only after rat microsomal enzyme activation and that of TMTD was increased after the microsomal enzyme activation.

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