• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.193-193
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• 1994

발암물질의 조기검색법 개발 및 chemoprevention연구의 일환으로 발암물질과 DNA 및 단백질의 공유결합체인 발암물질-DNA 및 -단백질 adduct를 연구하였다. 발암물질(예, 밴조피렌)-단백질 adduct에 관한 연구에서는 시료(단백질)에 soluble protease를 이용하는 간편하고 손쉬운 ELISA(Enzyme Linked Immunosorbent Assay)분석법을 확립했다. 발암물질(예,벤조피렌,아플라톡신 B1) -DNA 및 -단백질 adduct를 이용한 발암성 조기검색법의 개발을 Ames test 및 염색체이상시험과 비교 연구한 결과 본 연구에서 새로이 개발한 DNA 및 Protein-adduct형성 시험법은 저농도에서 고농도에 이르기까지 뚜렷한 용량-반응 관계를 나타냈으며 Ames test 및 Chromosomal test에서 일어날 수 있는 false positive나 false negative의 결과를 나타낼 우려가 없었다. 벤조피렌-DNA adduct를 이용한 chemoprevention 연구에서는 항산화제로 알려진 비타민 E,C 및 $\beta$-carotene을 시험한 결과 용량의존적으로 벤조피렌-DNA adduct 형성을 억제하였다.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.325-325
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• 1994

본 연구에서는 먼저 14종의 flavonoid화합물을 대상으로 발암물질로서 잘 알려져있는 benzo(a)pyrene[B(a)P]에 대한 소핵생성억제효과를 관찰하였다. 소핵시험을 이용한 유전독성억제실험에서 비적적 큰 활성을 보이는 flavonoid는 2,3 이중결합과 3,5,7-trihydroxyl기를 갖는 polyhydroxy flavonol화합물들이었다. 이중에서 galangin은 활성이 비교적 컸으며, 이같은 유전독성억제효과는 galangin투여시 B(a)P의 대사활성화가 감소되고 활성본태산물들의 DNA binding을 저해함으로서 나타났다. 한편, galangin은 대사활성화가 필요없는 1차 발암물질인 N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)에 의한 소핵생성도 감소시켰다. 이러한 galangin의 alkylating agent에 대한 유전독성억제효과는 calf thymus DNA를 이용한 실험에서 DNA의 메칠화를 저해하는 기전으로 나타나는 것으로 판단되었다. galangin은 mitouycin과 같은 DNA cross-linking agent에 의한 소핵생성에도 억제효과를 나타내었다. 특히 동시투여(simultaneous treatment)나 사후투여(post-treatment)시보다 사전투여(pre-treatment)시에 소핵생성억제효과가 컸으며 사전연속투여(multiple Pre-treatment)시에는 낮은 용량에서도 효과가 컸다. 이러한 저용량의 사전연용투여에 의한 유전독성억제효과들은 B(a)P나 MNNG에 대해서도 잘 나타났다.

• Korean Journal of Acupuncture
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• v.19 no.1
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• pp.7-13
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• 2002

The effects of Cnidium officinale Makino aqua-acupuncture solution (COMAS) and Cnidium officinale Makino water-extraced solution (COMWS) on the CYP1A1 activity and benzo[a]pyrene(B[a]P)-DNA adduct formation were examined. There were 6.8%, 12.1%, 15.1%, 18.3% and 22.6% inhibition in the activity of cytochrome 4501A1 enzyme with the treatment of $0.1{\times},\;0.5{\times},\;1{\times},\;3{\times},\;and\;5{\times}$ COMAS, respectively. At concentration of $0.1{\times}$ COMAS, the binding of $[^3H]B[a]P$ metabolites to DNA of NCTC-clone 1469 cell was significantly inhibited by 56.9%. These results suggest that COMAS has chemopreventive potential by inhibiting cytochrome P4501A1 activity and benzo[a]pyrene-DNA adduct formation.

• Journal of Korean Biological Nursing Science
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• v.12 no.3
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• pp.127-132
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• 2010

Purpose: The aim of this study is to evaluate the effect of Xanthium sibiricum Patr. on carcinogenesis. Method: Water extract from Xanthium sibiricum Patr. (XPW) was prepared and investigated for the potential antitumor activity and inhibition of benzo[a]pyrene-DNA adduct formation and free radical formation. Result: It was shown that the water possess considerable toxicity toward tumor cell lines. Concentration of XPW at 1.0 mg/mL and 2.5 mg/mL resulted in more than 30% inhibition of growth in HeLa cells. Toxicity of XPW to A549 revealed that 54% inhibition of growth at concentration of 2.5 mg/mL. At concentrations of 0.5 mg/mL, 1.0 mg/mL and 2.5 mg/mL of XPW, the binding of [$^3H$]B[a]P metabolites to DNA of human Chang cell was inhibited by 19%, 33%, and 41%, respectively. There 18% and 32% inhibition in the free radical formation with XPW at the concentration of 1.0 mg/mL and 2.5 mg/mL, respectively. Conclusion: Water extract from Xanthium sibiricum Patr. (XPW) has antitumor and cancer chemopreventive activities.

• Environmental Mutagens and Carcinogens
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• v.9 no.1
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• pp.1-12
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• 1989

To study the selective organospecific carcinogenesis by the specific chemical carcinogens, the breast cancer induction model by oral administration of 7, 12-dimethylbenzanthracene (DMBA) or by intravenous injection of N-methylni-trosourea (NMU) on female rats was analyzed. In the present experiment, we compared the effexts of ages on the chemical mammary carcinogenesis by studying the metabolic system of the carcinogenic activation, detoxification or DNA damage and repair. The breast tumor incidence was significantly higher in the young rats of 50 days old than in those of one year old rats. As an index of organospecific DNA damage or repair, the in vivo covalent binding index(CBI) of the specific organs by the specific chemical carcinogens was monitored. And for the analysis of carcinogenic activation, the quantity of cytochrome P450`s was determined with the respective type-specific monoclonal antibody, while the detoxication capacity was deduced by the activity monitoring of glutathione S-transferase (GST) and peroxidase. The skin tissues of the mammary region had the highest CBI with both of DMBA and NMU at 50 days of age. And there were contrasting differences in the contents of carcinogenic activation and detoxication system: that is, the content of T.C.D.D.-inducible cytochrome P450 was high, while the activities of GST and peroxidase was low in the mammary skin tissues at tumor prevalent age. These results led us to conclude that the molecular organospecific carcinogenesis, as illustrated with mammary carcinoge-nesis by DMBA and NMU, is operated probably through the differential capacity of the target tissues in the high carcinogenic activation, low detoxication and the low DNA repair function.

• Journal of Ginseng Research
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• v.23 no.2 s.54
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• pp.105-114
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• 1999

To investigate the effects of korean ginseng on the expression of transferrin receptor (TfR) in the liver cell membrane, we had carried out the experiments of $[^{3}H]thymidine$ uptake, $^{125}I-transferrin$ binding, and TfR mRNA expression in the liver after partial hepatectomy of normal and 3'-methyl-4-dimethylaminoa-zobenzene (3'-Me-DAB) treated rat with or without treatment of korean gingseng. $[^3H]thymidine$ uptake was not changed in the liver of 3'-Me-DAB or ginseng treated rat compared to that of control rat, but increased in that of partial hepatectomy of normal or 3'-Me-DAB treated rat. And this increased $[^{3}H]thymidine$ uptake was lowered slightly by the treatment of ginseng. Transferrin binding sites in the liver plasma membrane of ginseng treated rat with or without partial hepatectomy were similar, but increased in that of 3'-Me-DAB treated rat with or without partial hepatectomy compared to those of each control rat and these increased binding sites were reduced by ginseng treatment. Transferrin binding affinity (l/kd) was not changed by ginseng treatment, but tended to decrease in the liver of 3'-Me-DAB treated rat or in those after partial hepatectomy of all groups and reverse by ginseng treatment in 3'-Me-DAB treated rat. The expression of TfR mRNA was increased in the liver of 3'-Me-DAB treated rat with partial hepatectomy (peak at 24 hours), but lowered by ginseng treatment in this rat. From these results, it is suggested that korean ginseng has no effect on the increased expression of TfR with decreased affinity in the cell membrane of regenerated liver after partial hepatectomy of rat, but could inhibt that of 3'-Me-DAB treated rat through the regulation of DNA synthesis or TfR mRNA in partial.