• Title/Summary/Keyword: Mutagen X

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Application of X-Y Dissociation of Mice as the in vivo Assaying System for Environmental Mutagens (Mouse 제 1정모세포에서의 X-Y 염색체 조기 분리;in vivo 환경성 변이원 검출계로서의 응용 가능성)

  • 최영현;권용원;최병태;조운복;이원호
    • Toxicological Research
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    • v.11 no.1
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    • pp.51-55
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    • 1995
  • The present experiment was carried out to investigate whether X and Y chromosome dissociation in the primary spermatocytes of mice can be used as an in vivo assaying system that detect environmental mutagens. For this purpose, alkylating agents (EMS, MMS and MMC), which are strong mutagens, were administered to ICR male mice 12-15 weeks old. The mean frequencies of previously dissociated X-Y chromosomes and autosomes of the control group were 7.34-7.45% and 0.92-1.04%, respectively. The frequencies of X-Y dissociation in the mutagen-treated groups with 10.0 mM EMS and 5.0 mM MMS were about 3.3-4.6 times higher than that in the control group, but there were no significant differences in dissociation of autosomes in both the control and the mutagen-treated groups. These results suggest that X-Y dissociation in the primary spermatocytes of mice can be used as an in vivo short-term assaying system for environmental mutagens.

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Computational Study of Mutagen X

  • Cho, Seung-Joo
    • Bulletin of the Korean Chemical Society
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    • v.24 no.6
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    • pp.731-732
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    • 2003
  • Mutagen X (MX), 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone is one of the most potent directing acting mutagen ever tested in SAL TA100 assay. Although MX analogues have been synthesized, tested for mutagenicity and modeled by structure-activity relationship (SAR) methods, the mechanism of interaction of these compounds with DNA to produce their remarkable mutagenic potency remains unresolved. MX exists as an equilibrium mixture of both ring and open form in water. This equilibrium is very fast for Ames test. Because the mixture is not separable by experimental methods, it is not clear which one is really responsible for the observed mutagenicity. There have been many debates that which one is really responsible for the observed mutagenicity. We used ab initio methods for the MX analogues. It seems both ring and open form could react with DNA bases as electrophiles. However, every open form has consistently lower LUMO energy than corresponding ring form. It is reasonable to assume that the major reaction will go through via open form for MX analogues. This suggest that the open form is more likely really mutagenic.

3D QSAR (3 Dimensional Structure Activity Relationship) Study of Mutagen X

  • Yoon, Hae-Seok;Cho, Seung-Joo
    • Molecular & Cellular Toxicology
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    • v.1 no.1
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    • pp.46-51
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    • 2005
  • Mutagen X (MX) exists in our drinking water as the bi-products of chlorine disinfection. Being one of the most potent mutagen, it attracted much attention from many researchers. MX and its analogs are tested and modeled by quantitative structure activity relationship (QSAR) methods. As a result, factors affecting this class of compounds have been found to be steric and electrostatic effects. We tried to collect all the data available from the literature. The quantitative structure-activity relationship of a set of 29 MX was analyzed using Molecular Field Analysis (MFA) and Receptor Surface Analysis (RSA). The best models gave $q^{2}=0.918,\;r^{2}=0.949$ for MFA and $q^{2}=0.893,\;r^{2}=0.954$ for RSA. The models indicate that an electronegative group at C6 position of the furanone ring increases mutagenicity.

Influence of Mutagen at Meiotic Stage on Wheat Ploidy in Anther Culture (밀 감수분열기 Mutagen 처리가 약배양에 있어서 염색체 변이에 미치는 영향)

  • 박광근;강양순;하용웅;허한순
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.36 no.1
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    • pp.74-78
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    • 1991
  • This experiment was conducted to know the effects of mutagen treatments on callus induction, plant regeneration and their ploidy in the anther culture of wheat. The winter wheat cultivars, 'apos;and 'apos;Wonkwang'apos;, were treated at the mid or late-uninucreate stage under 4 different doses (100, 200, 500 and 1,000 rad.) of X-ray and 3 different levels(0.1, 0.2 and 0.3 mole) of Ethyl Methane Sulphonate. The anthers treated were set on the C$\_$17/medium for callus induction, and callus induced was transfered to 1/2 MS medium for plant regeneration. The mutagen treatments inhibited the callus induction but increased the plant regeneration in the callus which were induced from the anther set on the medium for the long time of 60 to 80 days. Also, the chromosome number to the regenerated plant varied largely by increasing of haploid plants(n=3x=21) and by occurring of aneuploidy having n=20 and n=22 of chromosome number.aried largely by increasing of haploid plants(n=3x=21) and by occurring of aneuploidy having n=20 and n=22 of chromosome number.

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Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Index Analysis (CoMSIA) Study of Mutagen X

  • Bang, Soo-Jin;Cho, Seung-Joo
    • Bulletin of the Korean Chemical Society
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    • v.25 no.10
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    • pp.1525-1530
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    • 2004
  • Mutagen X (MX) exists in our drinking water as the bi-products of chlorine disinfection. Being one of the most potent mutagen, it attracted much attention from many researchers. MX and its analogs are synthesized and modeled by quantitative structure activity relationship (QSAR) methods. As a result, factors affecting this class of compounds have been found to be steric and electrostatic effects. We tried to collect all the data available from the literature. With both CoMFA and CoMSIA various combinations of physiochemical parameters were systematically studied to produce reasonable 3-dimensional models. The best model for CoMFA gave $q^2$ = 0.90 and $r^2$ = 0.97, while for CoMSIA $q^2$ = 0.85 and $r^2$ = 0.94. So the models seem to be reasonable. Unlike previous result of CoMFA, in our case steric parameter alone gave the best statistics. Although the steric contribution was found to be the most important in both CoMFA and CoMSIA, steric parameter along with electrostatic parameter produced slightly better model in CoMSIA. Overall, steric contribution is clearly the most important single factor. However, when we compare chlorine and bromine substitution, chlorine substitution can be more mutagenic. This indicates that other factors such as electrostatic effect also influence the mutagenicity. From the contour maps, steric contribution seems to be focused on rather small area near C6 substituent of the furanone ring, rather than C3 substituent. Therefore the locality of steric contribution can play a significant role in mutagenicity.

Hologram Quantitative Structure Activity Relationship (HQSAR) Study of Mutagen X

  • Cho, Seung-Joo
    • Bulletin of the Korean Chemical Society
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    • v.26 no.1
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    • pp.85-90
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    • 2005
  • MX and its analogs are synthesized and modeled by quantitative structure activity relationship (QSAR) study including comparative molecular field analysis (CoMFA). As a result, factors affecting this class of compounds have been found to be steric and electrostatic effects. Because hologram quantitative structure activity relationship (HQSAR) technique is based on the 2-dimensional descriptors, this is free of ambiguity of conformational selection and molecular alignment. In this study we tried to include all the data available from the literature, and modeled with the HQSAR technique. Among the parameters affecting fragmentation, connectivity was the most important one for the whole compounds, giving good statistics. Considering additional parameters such as bond specification only slightly improved the model. Therefore connectivity has been found to be the most appropriate to explain the mutagenicity for this class of compounds.

Studies on X-Y Chromosome Dissociation Induced by Environmental Mutagens in Mouse (환경성 돌연변이원에 의한 Mouse의 X-Y 염색체 조기분리에 관한 연구)

  • 윤경희;이원호
    • Journal of Environmental Science International
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    • v.7 no.5
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    • pp.599-605
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    • 1998
  • The purpose of this work was to examine whether X-Y chromosome dissociation in the primary spermatocytes of mice could be used as an in vivo short-term assaying system that detect environmental mutagens. Four alkylating agents(EMS, MMS, MMC and MNNG) which were known as strong mutagens were administered to BALB/c male mice 3-4 months old. In the control group, the mean frequencies of previously dissociated X and Y chromosomes and autosomes were 7.17% and 2.12%, respectively. Compared to the control group, mutagen-treated groups have no significant differences in dissociation rate of autosomes, while these poops were about 1.2-2.5 times higher in the frequencies of X-Y dissociation. Generally, X-Y dissociation frequency increased consistently with the concentration of mutagens whereas the tendency of autosome dissociation frequency was variable among several mutagens. These results suggest that X-Y dissociation in the primary spermatocytes of mice is applicable as an vivo short-term assaying system for environmental mutagens. There were significantly distinct increase in dissociation of X-Y chromosome in both the hybrid and parents but the X-Y previous dissociation of hybrid appeared higher frequency than BALB /c and wild mice. These results indicate that the factor related to binding X-Y chromosome is specific to strains.

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Relationships between LET and RBE of lonizing Radiation in the induction of Somatic Mutations of Drosophila melanogaster

  • 유미애;정운혁;이원호
    • Environmental Mutagens and Carcinogens
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    • v.7 no.2
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    • pp.103-111
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    • 1987
  • The effects of LET (linear energy transfer) of radiation on the induction of somatic chromosome mutations or gene mutations of Drosophila melanogaster were studied. For detecting somatic chromosome mutations and gene mutations, Drosophila wing spot system and eye-color spot system were used, respectively. The frequencies of somatic chromosome mutations or gene mutations induced after third instar larval treatment with 23 MeV neutrons, thermal neutrons, X-rays were examined. From these data, the RBE(relative biological effectiveness) values of 23 MeV neutrons relative to X-rays for induction of somatic chromosome mutations or gene mutations were calculated. The present results suggest that high LET radiations are efficient than X-ray in producing not only somatic chromosome mutations but also gene mutations.

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