• Natural Product Sciences
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• 제8권4호
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• pp.162-164
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• 2002

The methanol extracts of 42 Korean indigenous plants were evaluated for the DNA strand-scission activity. As a result, the 17 extracts were found to be active in the criteria of $IC_{50}$}<$25\;{\mu}g/ml$. Among others, the MeOH extracts of Caesalpinia sappan and Mucuna birdwoodiana showed the most potent DNA strand-scission activity with $IC_{50}$ values of 5.9 and $4.9\;{\mu}g/ml$, respectively. Therefore, the partition and fractionation for C. sappan were performed and tested in the DNA strand-scission assay system for further bioassay-guided fractionation.

• Journal of Applied Biological Chemistry
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• 제43권3호
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• pp.156-160
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• 2000

The possible mechanism of the DNA strand breaking activity of the hot-water extract of Fructus Chaenomelis (dried fruit of Chaenomeles sinensis) in a closed circular duplex replica form DNA (RFI DNA) was studied through agarose gel electrophresis under various conditions. Induction of DNA strand scission by the hot-water extract of C. sinensis occurred in dose and time-dependent manners. $Cu^{2+}$ was indispensable for the induction of DNA strand breakage. Exogeneous chelating agents inhibited the DNA breaking activity, conforming the catalytic action of $Cu^{2+}$ on generation of free radicals responsible for oxidative damage. Antioxidant enzymes and some radical scavengers were used to investigate the major radical species triggering the DNA strand scission, demonstrating that a highest inhibitory activity was found in the presence of catalase, while less in the presence of tiron (a scavenger for superoxide radical), 2-aminoethyl-isothiuroniumbromide-HBr, cysteamine (scavengers for hydroxyl radical), and 1,4-diazabicyclo [2,2,2] octane (a scavenger for singlet oxygen) in decreasing order. The findings implied that oxygen radical species generated in presence of transition divalent cation during the oxidation of some compounds contained in the hot-water extract of C. sinensis is mainly responsible for inducing genotoxicity.

• Natural Product Sciences
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• 제9권2호
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• pp.105-108
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• 2003

During our research program to find DNA strand-scission agents from higher plants, the MeOH extracts of the stems of Mucuna birdwoodiana Tutcher. (Leguminosae) exhibited the most potent activity with an $IC_{50}$ value of $4.9\;{\mu}g/ml$. Thus, detailed laboratory investigation was performed, and led to the isolation of known compounds, $({\pm})$-catechin (1) and (-)-epicatechin(2) as active principles. Compounds 1 and 2 showed significant activity of DNA strand-scission with $IC_{50}$ values of 10.8 and $7.5\;{\mu}g/ml$, respectively (positive control, bleomycin: $IC_{50}\;3.3\;{\mu}g/ml$.

• Applied Biological Chemistry
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• 제40권4호
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• pp.307-312
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• 1997

유색미의 항암활성을 in vitro에서 조사하기 위한 기초실험으로서, 유색미 겨의 유기용매 추출물에 의한 DNA strand scission 및 발암 promotion의 억제효과를 조사하였다. 실험에는 유색미로 상해향혈나와 수원415호의 두 품종과 함께 대조구로 추청을 사용하였다. 품종별 변이원 억제활성은 70% 에탄올추출물 및 모든 유기용매 분획물에서 추청<상해향혈나<수원415호의 순서로 증가하였다. 그러나 DNA strand scission에 대한 억제활성은 70% 에탄올 추출물에서 상해향혈나<추청<수원415호의 순서로 증가하였다. 클로로포름 분획물에 대하여 조사한 결과, 상해향혈나에는 거의 DNA strand scission을 억제하는 활성이 없었으며, 예상과는 달리 추청은 오히려 상해향혈나보다 약간 활성이 높았다. 그리고 수원415호의 클로로포름분획물은 70%에탄올 추출물의 경우와 비슷한 수준의 강한 억제활성을 보였다(약 50% 억제). 발암 promotor에 의하여 유도된 Epstein-Barr 바이러스의 early diffusible antigen의 발현수준을 지표로 하여 70% 에탄올 추출물의 발암 promotion의 억제효과를 측정한 결과, 추청<상해향혈나< 수원415호의 순서로 억제활성이 높아짐을 알 수 있었다. 세 품종 모두의 클로로포름분획물에서 발암 promotion을 완전히 차단하는 효과가 발견되었지만, 세포독성이 동반되지 않은 promotion에 대한 억제효과는 수원415호에서만 유일하게 관찰되었다.

• Archives of Pharmacal Research
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• 제26권2호
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• pp.147-150
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• 2003

To find anticancer agents from higher plants, DNA strand-scission assay method was employed for bioassay-guided fractionation as well as for screening the crude extracts. During the screening, an ethyl acetate extracts of the heartwood of Caesalpinia sappan L. (Leguminosae) exhibited potent DNA strand-scission activity. Therefore, the ethyl acetate extracts of the dried heartwood of C. sappan was subjected to the bioassay-guided fractionation, which led to the isolation of a known compound, brazilin (1) as the active constituent. In addition, caesalpine J (2) was also isolated as an inactive constituent.

• 한국식품과학회지
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• 제30권4호
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• pp.964-969
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• 1998

곡류 및 두류에탄올 추출물의 발암억제효과를 검토하기 위하여 10종의 곡류를 선정해서 70% 에탄올 추출물을 얻은 다음 항변이활성, 항산화활성, DNA 손상 억제효과 및 발암 promotion 억제효과를 비교하였다. E. coli PQ 37 균주를 이용한 SOS chromotest에 의해서 항변이활성을 검색한 결과 화곡류에 비해 두류의 활성이 높은 경향을 보였으며, 특히 검정콩과 팥의 항변이활성이 높았다. 변이원 물질로 사용되는 mitomycin C는 DNA의 strand scission 현상을 유발함으로써 DNA의 손상을 초래하게 되므로, 이의 처리를 통하여 쌀겨 및 곡류 추출물이 DNA의 손상을 억제하는 정도를 측정하였다. 곡류중 조와 율무의 70% 에탄올 추출물의 DNA 손상억제 효과가 큰 것으로 관찰되었으며 두류중에는 검정콩과 흰콩의 70% 에탄올 추출물에서 강한 DNA 손상억제효과를 관찰하였다. 곡류 및 두류 에탄올추출물의 DNA 손상억제효과가 확인되었으므로 이들의 효과를 검증하기 위하여 Linoleic acid model system을 이용한 항산화활성을 측정하였다. DNA 손상억제효과와 유사하게 두류의 항산화 효과가 컸으며 율무>검정콩>조>흰콩>보리>현미의 순이였다. Epstein-Barr Virus (EBV)활성화 시험법을 적용하여 곡류 및 두류 에탄올추출물의 발암 promotion 억제 효과를 측정한 결과, 수수와 메밀의 발암 promotion 억제 효과가 관찰되었고 두류 중 검정콩과 팥에 있어서 강한 억제효과가 관찰되었다.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.255.1-255.1
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• 2003

During our research program to find DNA strand-scission agents from higher plants, the MeOH extracts of the wood bark of Mucunar birdwoodiana Tutcher. (Leguminosae) exhibited the most potent activity with an IC$\^$50/ value of 4.9 $\mu\textrm{g}$/$m\ell$. Thus, detailed laboratory investigation was performed, and led to the isolation of the known compounds, catechin(1) and epicatechin(2) as the active principles. (omitted)

• Archives of Pharmacal Research
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• 제26권2호
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• pp.124-127
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• 2003

Four known prenylated flavonoids, artonins E (1) and O (2), artobiloxanthone (3), and cycloartobiloxanthone (4), were isolated from the stem bark of Artocarpus kemando by bioassayguided fractionation using the DNA strand-scission and the KB cytotoxicity assays as monitors. Compounds 1 and 3 exhibited strong DNA strand-scission activity, and all four compounds were found to be cytotoxic.

• Applied Biological Chemistry
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• 제48권3호
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• pp.222-227
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• 2005

특수미인 거대배아미와 유색미의 발아처리에 의한 항돌연변이 활성의 변화를 평가하고자, 70% 에탄올 추출물이 in vitro에서 산화적 손상에 의한 DNA strand scission을 억제하는 효과와 함께 E. coli 및 V79 배양세포에 화학적으로 유발된 돌연변이에 대한 억제효과를 측정하였다. Mitomycin C로 유발된 돌연변이에 대한 억제활성을 E. coli에서 SOS chromotest로 조사한 결과, 활성은 발아유색미(40.4%) > 발아거대배아미(37.1%) > 무발아유색미(35.5%) > 발아현미(15.7%) > 무발아거대배아미(14.0%) > 무발아현미(0.8%)의 순서였다. Mitomycin C가 유도한 DNA strand scission에 대한 억제 효과는 무발아유색미 > 무발아거대배아미 > 발아유색미 > 발아현미 > 무발아현미 > 발아 거대배아미로 나타났다. V79 세포주에서 4-NQO로 유도된 6-TG 저항성 colony의 형성을 저해하는 활성을 지표로 항돌연변이 활성을 조사한 결과, 발아거대배아미(53.2%) > 무발아유색미(40.0%) > 무발아현미(21.2%) > 발아현미(14.4%) > 무발아거대배아미(0.23%)의 순서로 돌연변이를 저해하였는데, 발아유색미는 돌연변이를 촉진하는 것으로 나타났다(-69%).

• 대한의생명과학회지
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• 제15권1호
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• pp.1-8
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• 2009

Human genomic DNA is continuously attacked by oxygen radicals originated from cellular metabolic processes and numerous environmental carcinogens. 2-deoxyribonolactone (dL) is a major type of oxidized abasic (AP) lesion implicated in DNA strand scission, mutagenesis, and formation of covalent DNA-protein crosslink (DPC) with DNA polymerase (Pol) ${\beta}$. We show here that human DNA polymerase (Pol)${\iota}$ and mitochondrial $Pol{\gamma}$ give rise to stable DNA-protein crosslink (DPC) formation that is specifically mediated by dL lesion. $Pol{\gamma}$ mediates DPC formation at the incised dL residue by its 5'-deoxyribose-5-phosphate (dRP) lyase activity, while $Pol{\gamma}$ cross links with dL thorough its intrinsic dRP lyase and AP lyase activities. Reactivity in forming dL-mediated DPC was significantly higher with $Pol{\gamma}$ than with $Pol{\iota}$. DPC formation by $Pol{\gamma}$, however, can be reduced by an accessory factor of $Pol{\gamma}$ holoenzyme that may attenuate deleterious effects of crosslink adducts on mitochondrial DNA. Comparative kinetic analysis of DPC formation showed that the rate of DPC formation with either $Pol{\iota}$ or $Pol{\gamma}$ was lower than that with $Pol{\beta}$. These results revealed that the activity of catalytic lyase in DNA polymerases determine the efficiency of DPC formation with dL damages. Irreversible crosslink formation of such DNA polymerases by dL lesions may result in a prolonged strand scission and a suicide of DNA repair proteins, both of which could pose a threat to the genetic and structural integrity of DNA.