• YAKHAK HOEJI
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• v.54 no.1
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• pp.67-74
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• 2010

Some of the benzopyrene (BP)-DNA adduct are known to build intercalated motif between flanking base pairs in damaged DNA depending on the structural condition. The size of benzopyrene itself is definitely not comparable with any of the DNA bases and thus the question whether the lesion of some base pair by insertion of benzopyrene can happen with or without a dramatic distortion of the helical structure is a highly interesting theme. In this work we used a molecular dynamics simulation based on the theory of molecular mechanics. The specific consequences about the structural properties of the intercalated structures and benzopyrene motif in minor groove of the double helix are deduced after 5 ns simulation time.

• Environmental Analysis Health and Toxicology
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• v.21 no.4 s.55
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• pp.375-380
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• 2006

Endocrine disrupting chemicals (EDC) have been emphasized due to their threats in human health. Waste incinerator emission has been emphasized as a source of EDC including polychlorinateddibenzofurans(PCDD/F) and other carcinogenic polycyclic aromatic hydrocarbons (PAHs). Urinary 1-hydroxypyrene (1-OHP) has been used as an exposure biomarker for the PAHs. On the other hand, etheno-DNA adducts, e.g. 1, $N^6-ethenodeoxyadenosine({\varepsilon}dA)$, has been developed as an useful effective or response biomarker for carcinogenesis. Thus, I investigated association between urinary 1-OHP and ${\varepsilon}dA$ levels due to distance from an incinerator which was built more 10 years ago in the middle of a farm in P city. I designated the EDC-high and low exposed group due to distance from the incinerator, i.e. within 2.5km and $5.0{\sim}7.5km$ from the incinerator, respectively. The study subjects were age and sex-matched males and females (mean age, $61.3{\pm}9.6$ yrs; total 40 persons, male, 10; female, 10 for the each group). Urinary 1-OHP and ${\varepsilon}dA$ were analyzed with HPLC-FD and IP-HPLC-FD, respectively. As results, the distance from the incinerator was not associated with urinary 1-OHP nor ${\varepsilon}dA$ levels (p=0.43 and 0.82, respectively). On the other hand, urinary ${\varepsilon}dA$ levels were significantly higher in the hyperlipidemia group (N=10) than normal group (N=30). In conclusion, urinary 1-OHP nor ${\varepsilon}dA$ levels can not be suggested as an incinerator-related exposure nor effective biomarker. However, not only distance from the incinerator bot also systemic approaches including wind and soil contamination are required to assume exposure levels of incinerator-related EDC.

• Journal of Environmental Health Sciences
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• v.28 no.4
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• pp.6-11
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• 2002

3.3'-Dichlorobenzidine(DCB) has be shown carcinogenic in several animals, and the development of non-invasive biomonitoring method in workers exposed with it is a very important subject. DNA adduct is a good biomarker for biomonitoring about carcinogens exposure, and lymphocytes is a good non-invasive samples. So we studied to analyze metabolites in blood lymphocytes of female Sprague-Dawley rats exposed orally with DCB(20, 30, and 40 mg/kg wt.) for 3 weeks. For analysis of them, we isolated DNA adducts from blood lymphocytes by using the enzymes method in /sup 32/P-postlabeling, and measured them by using gas chromatography/mass spectrometry-selected ion monitoring(GC/MS-SIM). 4-aminobiphenyl and phenanthrene-d/sub 10/ were added as internal standard for blank sample. Standard metabolites of DCB were synthesized with using pyridine and acetic acid which were promoter and controller in acetylation of DCB. And they were used for calibration curve. Our results showed two kinds of metabolites in DNA adducts of blood lymphocytes. They were N-acetyl 3,3'-dichlorobenzidine(acDCB) and N,N'-diacetyl 3,3'-dichiorobenzidine(di-acDCB ). They were combined with DNA at the same time as an acetyl of it was removed. So we measured DCB and acDCB for two kinds of metabolites in DNA adducts of blood lymphocytes. Our results showed the levels of DCB were 1.46∼2.26 times more than that of acDCB. And also the levels of metabolites in 20, 30 and 40 mg/kg wt. were gradually increased with going days from 1st to 3rd week. They are 1.66, 1.38 and 0.90 times in total metabolites, 1.76, 1.49 and 1.02 times in DCB, and 1.51, 1.22 and 1.28 times in acDCB. In conclusion, the results of this study showed DCB exposed to rats formed DNA adduct in blood lymphocytes after acetylated to N-acetyl 3.3'-dichloro benzidine(acDCB) and N,N'-diacetyl 3,3'-dichlorobenzidine(di-acDCB), and they could be analyzed by us ing gas chromatography/mass spectrometry-selected ion monitoring(GC/MS-SIM).

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2003.05a
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• pp.59-59
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• 2003

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2001.10b
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• pp.46-47
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• 2001

• BMB Reports
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• v.33 no.3
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• pp.268-275
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• 2000

In contrast to the pyrimidine (6-4)pyrimidone photoproduct [(6-4) adduct], its Dewar valence isomer (Dewar product) is low mutagenic and produces a broad range of mutations with a 42 % replicating error frequency. In order to determine the origin of the mutagenic property of the Dewar product, we used experimental NMR restraints and molecular dynamics to determine the solution structure of a Dewar·lesion DNA decamer duplex, which contains a mismatched base pair between the 3'-T residue and an opposed G residue. The 3'-T of the Dewar lesion forms stable hydrogen bonds with the opposite G residue. The helical bending and unwinding angles of the DW/GA duplex, however, are much higher than those of the DW/AA duplex. The stable hydrogen bonding of the G 15 residue does not increase the thermal stability of the overall helix. It also does not restore the distorted backbone conformation of the DNA helix that is caused by the forming of a Dewar lesion. These structural features implicate that no thermal stability, or conformational benefits of G over A opposite the 3'-T of the Dewar lesion, facilitate the preferential incorporation of an A. This is in accordance with the A rule during translesion replication and leads to the low frequent $3'-T{\rightarrow}C$ mutation at this site.

• 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.

• 대한예방의학회:학술대회논문집
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• 1999.10a
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• pp.94-95
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• 1999

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.41-42
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• 2001

The chemopreventive effect of tea against 2-amino-l-methyl-6-phenylimidazo［4, 5-b ］pyridine (PhIP)-DNA adduct formation and its mechanism were studied. Rats were exposed to freshly prepared aqueous extracts of green tea (3% w/v) as the sole source of drinking water for 10 days prior to administration with a single dose of PhIP (10 mg/kg body wt) by oral gavage. PhIP-DNA adducts in the liver, colon, heart, and lung were measured using the $^{32}$ P-postlabelling technique.(omitted)

• Proceedings of the Korean Society of Toxicology Conference
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• 2006.11a
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• pp.34-45
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• 2006

Chemical toxicants are metabolically converted to numerous metabolites in the body. Toxicokinetic characteristics of metabolites could be therefore used as biomarker of exposure for human risk assessment. Biologically based dose response (BBDR) model was proposed for future direction of risk assessment. However, this area has not been developed well enough for human application. Benzo(a)pyrene (BP), for example, is a well-known environmental carcinogen and may produce more than 100 metabolites and BPDE-DNA adduct, a covalently bound form of DNA with benzo(a)pyrene diolepoxides (BPDES), has been applied to qualitatively or quantitaively estimate human exposure to BP. In addition, di(2-ethylhexyl) phthalate (DEHP), a widely used plasticize. in the polymer industry, is one of endocrine-disrupting chemicals (EDCs) and has been monitored in humans using urinary or serum concentrations of DEHP or its monomer MEHP for exposure and risk assessment. However, it is difficult to estimate the actual level of toxicants using these biomarkers in humans using. This presentation will discuss a methodology of exposure and risk assessment by application of metabolic profiling kinetics.