• Journal of Ginseng Research
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• 제35권3호
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• pp.339-343
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• 2011

Polycyclic aromatic hydrocarbons (PAHs) are well known environmental carcinogens. PAH metabolites, especially BaP-7,8- dihydrodiol, 9,10 epoxide, initiate carcinogenesis via high specificity binding to DNA to form DNA adducts. The Korean red ginseng (KRG) from Panax ginseng has been suggested to protect against damages due to PAH exposure but the mechanism is unknown. Therefore, we investigated effects of KRG on PAH exposure using toxicokinetic methods and changes of PAH-induced oxidative damage during a 2 week-clinical trial (n=21 healthy young female, $23.71{\pm}2.43$ years). To analyze antioxidative effects of KRG, we measured changes in the levels of urinary malondialdehyde (MDA) before and after KRG treatment. We observed a significant positive association between levels of urinary MDA and 1-hydroxypyrene, a biomarker of PAH exposures (slope=1.47, p=0.03) and confirmed oxidative stress induced by PAH exposures. A reverse significant correlation between KRG treatment and level of urinary MDA was observed (p=0.03). In summary, results of our clinical trial study suggest that KRG plays a significant role in antioxidative as well as toxicokinetic pathways against PAHs exposure.

• 한국자기공명학회논문지
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• 제3권1호
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• pp.60-70
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• 1999

The pyrimidine(6-4) pyrimidone photoproduct [(6-4) adduct] is one of the major photoproducts induced by UV irradiation of DNA and occurs at TpT sites. The (6-4) adduct is highly mutagenic and specific during translesion replication. The marked preference for insertion of A opposite the 5'-T and G opposite the 3--T of the (6-4) adducts leads to a predominantly 3'-T\longrightarrowC transition with 85% replicating error rate. In order to obtain insight into the origin of 3'-T\longrightarrowC transition induced by the (6-4) adduct, we have performed one - and two-dimensional NMR experiment. The 3'-Tof the (6-4) lesion forms the stable hydrogen bonding to the imino proton of an opposed G, which stabilizes the overall helix and diminishes the highly distorted conformation caused by the (6-4) lesion in the (6-4)/AA duplex. We proposed that the greater insertion of a G over an A opposite the 3'-T of the (6-4) lesion These results may account for the greater preference for the insertion of a G over a A opposite the 3'-T of the (6-4) lesion. Thus this insertion leads to the highly specific 3'-T\longrightarrowC multation at the (6-4) lesion site.

• 대한두경부종양학회지
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• 제22권2호
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• pp.117-122
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• 2006

Background and Objectives : Thyroid carcinoma is the sixth commonest cancer in Korea and the papillary carcinoma is the most common type(88%) of the malignant thyroid tumors. Bulky DNA adducts formed by the carcinogens are repaired by DNA repair process, but failure to repair this DNA damage can cause mutations in oncogenes and tumor suppressor genes resulting in tumor formation. The xeroderma pigmentosum group C(XPC) gene is essential for this repair procedure and the XPC-PolyAT(PAT) polymorphisms may alter DNA repair capacity(DRC) and genetic susceptibility to cancer. Subjects and Methods : In a case-control study of 113 Korean patients with pathologically diagnosed thyroid papillary carcinoma and 65 control subjects, we investigated the association between the three XPC-PAT gene polymorphisms and thyroid papillary cancer susceptibility. Results : The frequency of the variant XPC-PAT allele was lower in the cases(0.349) than in the controls (0.423), but the difference was not significant(p=0.140). Using logistic regression adjusting for age and sex, risk for thyroid papillary cancer was not increased in the XPC-PAT-/+ and XPC-PAT+/+ compared to XPCPAT-/-(adjusted overall odds ratio[95% confidence intervals;95%CI]=0.52[0.26-1.03] and 0.62 [0.22-1.75], respectively; trend test, p=0.167). Conclusion : There are no relationship between the XPC-PAT polymorphism and the risk of thyroid papillary carcinoma in Korean population. Based on our results, XPC-PAT polymorphism do not modulate genetic susceptibility to thyroid papillary cancer.

• 한국식품위생안전성학회지
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• 제13권3호
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• pp.243-251
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• 1998

백삼(Pampx ginseng C.A. Meyer, 4년근)을 가루로 한 다음 petroleum ether로 24시간 추출 후 감압 농축시켜 인삼 석유에텔추출물(GPE)로 하였다. 이때 GPE의 수율은 평균 2.24%였다. 또한 GPE를 petroleum ether 소량에 녹이고 petroleum ether:ether 용매계열로 silicagel column chromatography에 의한 partition을 실시하여 P1, P2, P3 , P4, P5의 5개의 분획을 얻었다. 본 실험에서는 소핵생성 물질인 N-methyl-N-nitrosourea(MNU) 및 benzo(a) pyrene[B(a)P]를 이용하여 소핵생성억제실험을 하였따. 상기의 5가지 분획 중에서 MNU에 대해서는 GPE, P1, P2에서 억제효과가 나타났다. 한편, B(a)P에 대해서는 GPE, P1, P2, P3 , P4, P5 모두에게 억제효과를 나타내었다. 그러나 여러 가지 활성을 보인 분획 중에서 여러 가지 양성대조물질들에 대해서 가장 두드러져 보이는 것은 P2였다. P2는 MNU, B(a)P 모두에 대해서 GPE와 유사한 억제경향을 보이면서 억제활성은 크게 나타난T다. EK라서 P2가 GPE가 보이는 소핵생성억제효과에 깊은 관련이 있는 물질로 판단되었다. 이와 같은 유전독성억제효과의 작용기전을 알기 위하여 B(a)P의 대사에 미치는 영향을 연구한 결과 GPE와 P2는 S-9 mix에 의해 유도된 B(a)P 대사를 억제시켰으며, DNA-B(a)P binding도 감소시켰다. 한편, MNU에 의한 DNA binding 과 O6-methyl guanine 및 7-methyl guanine 생성에 있어서도 억제적인 경향을 나타내었다. 따라서 GPE와 P2는 B(a)P와 같은 2차 발암 물질과 MNU와 같은 알킬화제에 의한 유전독성을 활성대사억제 및 methylation 억제 , DNA binding 억제 등의 기전으로 감소시키고 있는 것으로 판단되었다. 한편, 소핵생성억제 효과에서 가장 활성이 좋았던 P2를 NMR과 GC/MS결과, aliphatic ketone류의 혼합물로서 주성분은 분질량 330과 386의 두 개 물질이 함유되어 있는 혼합물이었으며 향후 계속적으로 분리 동정이 필요한 물질이다.

• 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.246.2-247
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• 2003

It has been reported that 2-bromopropane might be a causative agent for reproductive toxicity and have immunotoxic effects. 1-Bromopropane known as an alternative to ozone depleting solvents, which has structural similarity to 2-bromopropane, has been reported to be neurotoxic to rats in long-term inhalation exposure. (omitted)

• Bulletin of the Korean Chemical Society
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• 제25권12호
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• pp.1757-1763
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• 2004

A new series of nickel(II), cobalt(II)/(III) and copper(II) complexes of 14, 15 and 16-membered of macrocyclic ligands have been prepared and characterized by elemental analyses, IR, UV-VIS and $^1H-NMR$ spectra, magnetic susceptibilities, conductivities, DTA and ESR measurements. Molar conductances in DMF solution indicate that, the complexes are nonelectrolytes except (9-12) complexes. The electronic spectra show that, all complexes are square planar or distorted octahedral geometry. The ESR spectra of solid complexes (4), (8) and (11) show square planar of axial type symmetry $(d_{x2-y2})$ with considerable covalent bond character. However, complex (12) shows a spectrum of octahedral geometry with $d_{z2}$ ground state. Complex (12) shows exploitation in reducing the amount of electron adducts formed in DNA during irradiation with low radiation products.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.6967-6972
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• 2015

Background: Cigarette smoking and tobacco chewing are common modes of consuming tobacco all over the world. Parents need to be aware that germ cell integrity is vital for birth of healthy offspring as biological parenting begins much before birth of a child and even before conception. The present study was conducted to determine the etiology of non-familial sporadic heritable retinoblastoma (NFSHRb), by evaluating oxidative sperm DNA damage in fathers due to use of tobacco (smoking and chewing). Materials and Methods: We recruited 145 fathers of NFSHRb children and 53 fathers of healthy children (controls) in the study. Tobacco history was obtained by personal interview. Seminal reactive oxygen species (ROS) in semen, sperm DNA fragmentation index (DFI) and 8 hydroxy 2' deoxyguanosine (8-OHdG) levels in sperm were evaluated. The RB1 gene was screened in genomic blood DNA of parents of children with NFSHRb and controls. Odds ratios (ORs) derived from conditional logistic regression models. Results: There was significant difference in the levels of ROS (p<0.05), DFI (p<0.05) and 8-OHdG (p<0.05) between tobacco users and non-users. The OR of NFSHRb for smokers was 7.29 (95%CI 2.9-34.5, p<0.01), for tobacco chewers 4.75 (2.07-10.9, p<0.05) and for both 9.11 (3.79-39.2; p<0.01). Conclusions: This study emphasizes the adverse effect of tobacco on the paternal genome and how accumulation of oxidative damage in sperm DNA may contribute to the etiology of NFSHRb. In an ongoing parallel study in our laboratory, 11 of fathers who smoked underwent. Meditation and yoga interventions, showed significant decline in levels of highly mutagenic oxidised DNA adducts after 6 months. Thus our lifestyle and social habits impact sperm DNA integrity and simple interventions like yoga and meditation are therapeutic for oxidative damage to sperm DNA.

• 대한골관절종양학회지
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• 제15권1호
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• pp.13-25
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• 2009

서론: $O^6$-methylguanine-DNA methyltransferase (MGMT)는 DNA 염기 손상에 의해 형성된 $O^6$-methylguanine에서 알킬기를 제거하여 DNA 염기 손상을 복구하는 역할을 한다. MGMT의 후생유전적 불활성화가 인체 종양에서 보고되고 있으며, 항암 치료에 대한 저항성에 영향을 주는 요소로 알려져 있다. 본 연구에서는 연부조직육종에서 이러한 MGMT 불활성화가 미치는 영향에 대해 살펴보고자 하였다. 재료 및 방법: 총 62예의 연부조직육종조직에서 메틸화 특이 중합효소연쇄반응을 이용하여 MGMT 유전자의 촉진자 부위 메틸화 정도를 알아보고, 면역조직화학염색을 통하여 MGMT 단백 발현의 소실 양상을 살펴보았다. 결과: MGMT 단백 발현 소실은 진행성 병기(p=0.000), 조직학적 고등급(p=0.005), 종양의 재발 또는 전이(p=0.011), 그리고, 낮은 생존률(p=0.017)과 통계학적 유의성을 보였다. MGMT 유전자 촉진자 부위 메틸화는 조직학적 고등급, 종양의 재발 또는 전이, 그리고, 낮은 생존률과 관련성을 보였다. 또한, MGMT 단백 발현의 소실은 MGMT 유전자 촉진자 부위 과메틸화와 높은 상관성을 나타내었다(p=0.000). 결론: 본 연구는 MGMT 단백 발현의 소실과 MGMT 유전자 촉진자 부위 과메틸화가 연부조직 육종에서 흔히 발생하며 종양의 공격적인 양상 및 나쁜 예후와 관련성이 있다는 것을 보여준다. 또한 MGMT 단백 발현의 소실은 대개 MGMT 유전자 촉진자 부위 과메틸화로 인해 발생한다는 사실을 보여주고 있다.

• Toxicological Research
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• 제25권2호
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• pp.85-92
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• 2009

4,4'-Methylenedianiline (MDA) is an aromatic amine that is widely used in the industrial synthetic process. Genotoxic MDA forms DNA adducts in the liver and is known to induce liver damage in human and rats. To elucidate the molecular mechanisms associated with MDA-induced hepatotoxicity, we have identified genes differentially expressed by microarray approach. BALB/c male mice were treated once daily with MDA (20 mg/kg) up to 7 days via intraperitoneal injection (i.p.) and hepatic damages were revealed by histopathological observation and elevation of serum marker enzymes such as AST, ALT, ALP, cholesterol, DBIL, and TBIL. Microarray analysis showed that 952 genes were differentially expressed in the liver of MDA-treated mice and their biological functions and canonical pathways were further analyzed using Ingenuity Pathways Analysis (IPA). Toxicological functional analysis showed that genes related to hepatotoxicity such hyperplasia/hyperproliferation (Timp1), necrosis/cell death (Cd14, Mt1f, Timp1, and Pmaip1), hemorrhaging (Mt1f), cholestasis (Akr1c3, Hpx, and Slc10a2), and inflammation (Cd14 and Hpx) were differentially expressed in MDA-treated group. This gene expression profiling should be useful for elucidating the genetic events associated with aromatic amine-induced hepatotoxicity and for discovering the potential biomarkers for hepatotoxicity.

• Toxicological Research
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• 제21권2호
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• pp.99-105
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• 2005

Photo-mutagenic compounds have been known to alter skin cancer rates by acting as initiators or by affecting subsequent steps in carcinogenesis. The objectives of this study are to investigate the utility of photo-chromosomal aberration (photo-CA) assay for detecting photo-clastogens, and to evaluate its ability to predict rodent photocarcinogenicity. Photo-CA assay was performed with five test substances that demonstrated positive results in photo-carcinogenicity tests: 8-Methoxypsoralen (photoactive substance that forms DNA adducts in the presence of ultraviolet A irradiation), chlorpromazine (an aliphatic phenothiazine an alpha-adrenergic blocking agent), lomefloxacin (an antibiotic in a class of drugs called fluoroquinolones), anthracene (a tricyclic aromatic hydrocarbon a basic substance for production of anthraquinone, dyes, pigments, insecticides, wood preservatives and coating materials) and Retinoic acid (a retinoid compound closely related to vitamin A). For the best discrimination between the test substance-mediated genotoxicity and the undesirable genotoxicity caused by direct DNA absorption, a UV dose-response of the cells in the absence of the test substances was firstly analyzed. All 5 test substances showed a positive outcome in photo-CA assay, indicating that the photo-CA test is very sensitive to the photo-genotoxic effect of UV irradiation. With this limited data-set, an investigation into the predictive value of this photo-CA test for determining the photo-carcinogenicity showed that photo-CA assay has the high ability of a test to predict carcinogenicity. Therefore, the photo-CA test using mammalian cells seems to be a sensitive method to evaluate the photo-carcinogenic potential of new compounds.