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내분비계 교란물질의 검출계를 이용한 γ-HCH의 미생물에 의한 중간대사산물에 대한 내분비계교란 활성의 평가
이행석,박주석,조은민,문명숙,太田明德,류재천 대한상하수도학회 2003 상하수도학회지 Vol.17 No.1
To develop an efficient degradation system for Endocrine disruptors (EDs), it is necessary to have a good system to evaluate rapidly and accurately endocrine-disrupting activities of suspected chemicals and their degradation products. We previously constructed a co-expression system of GAL4 DNA binding domain (DBD)-human estrogen receptorβ ligand binding domain (hERβ LBD) and Gal4p transcriptional activation domain (TAD)-co-activator SRC1 in Saccharomyces cerevisiae with a chromosome-integrated lacZ reporter gene under the control of CYC1 promoter and GAL4 binding site (Upstream Activating Sequence, UAS). Expression of this reporter gene was dependent on the presence of estrogen or endocrine disruptors in the culture medium. Furthermore, the extent of transcriptional activation by those chemicals correlated with their estrogenic activities measured by other assay systems, indicating that this assay system is efficient and reliable for measuring estrogenic activity. We applied this assay system to measure estrogenic activity of microbial degradation products of γ-hexachlorocyclohexane (γ-HCH) by Sphingomonas paucimobilis. Among the γ-HCH metabolites, 2,5-dichlorohydroquinone (2,5-DCHQ) and chlorohydroquinone (CHQ) had similar estrogenic activities to the original chemical, but hydroquinone (HQ), a metabolite at later stage, had no activity at the concentration of 10^-4M, showing the necessity of evaluation of intermediate metabolites in microbial degradation systems.
이행석(Haeng-Seog Lee),조은민(Eun-Min Cho),류재천(Jae-Chun Ryu) 한국환경성돌연변이발암원학회 2002 한국환경성돌연변이·발암원학회지 Vol.22 No.3
Endocrine disruptors (EDs) are the chemicals that affect endocrine systems through activation or inhibition of steroid hormone response. It is necessary to have a good system to evaluate rapidly and accurately endocrine-disrupting activities of suspected chemicals and their degradation products. The key targets of EDs<br/> are nuclear hormone receptors, which bind to steroid hormones and regulate their gene transcription. We constructed a co-expression system of Gal4p DNA binding domain (DBD)- ligand binding domain of human estrogen receptor α or β, and Gal4p transactivation domain (TAD)-co-activator AIB-1, SRC-1 or TIF-2 in Saccharomyces cerevisiae with a chromosome-integrated lacZ reporter gene under the control of CYC1 promoter and Gal4p binding site (GAL4 upstream activating sequence, GAL4UAS). Expression of this reporter gene was dependent on the presence of estrogen or EDs in the culture medium. We found that the two-hybrid system with combination of the hERβLBD and co-activator SRC-1 was most effective in the xenoestrogen-dependent induction of reporter activity. The extent of transcriptional activation by those chemicals correlated with their estrogenic activities measured by other assay systems, indicating that this assay system is efficient and reliable for measuring estrogenic activity. The data in this research demonstrated that the yeast detection system using steroid hormone receptor and co-activator is a useful tool for identifying chemicals that interact with steroid receptors.
인자분석을 이용한 광주지역 초미세먼지(PM<sub>2.5</sub>)의 특성 연구
이세행 ( Se-haeng Lee ),이경석 ( Kyung-seog Lee ),윤상훈 ( Sang-hoon Yoon ),양윤철 ( Yoon-cheol Yang ),박지영 ( Ji-young-park ),배석진 ( Seok-jin Bae ),이대행 ( Dae-haeng Lee ) 한국환경과학회 2019 한국환경과학회지 Vol.28 No.4
The objective of this study was to estimate the trends of air quality in the study area by analyzing monthly and seasonal concentration trends obtained from sampled data. To this aim, the mass concentrations of PM<sub>2.5</sub> in the air were analyzed, as well as those of metals, ions, and total carbon within the PM<sub>2.5</sub>. The mean concentration of PM<sub>2.5</sub> was 22.7 ㎍/㎥. The mass composition of PM<sub>2.5</sub> was as follows: 31.1% of ionic species, 2.2% of metallic species, and 26.7% of carbonic species (EC and OC). Ionic species, especially sulfate, ammonium, and nitrate, were the most abundant in the PM<sub>2.5</sub> and exhibited a high correlation coefficient with the mass concentration of PM<sub>2.5</sub>. Seasonal variations of PM<sub>2.5</sub> showed a similar pattern to those of ionic and metallic species, with high concentrations during winter and spring. PM2.5 also had a high correlation with the ionic species NO<sub>3</sub><sup>-</sup> and NH<sub>4</sub><sup>+</sup>. In addition, NH<sup>4</sup><sup>+</sup> was highly correlated with NO<sub>3</sub><sup>-</sup>. Through factor analysis, we identified four controlling factors, and determined the pollution sources using the United States Environmental Protection Agency(U.S. EPA) pollution profile. The first factor, accounting for 19.1% of PM<sub>2.5</sub> was attributed to motor vehicles and heating-related sources: the second factor indicated industry-related sources and secondary particles, and the other factors indicated soil, industry-related and marine sources. However, the pollution profile used in this study may be somewhat different from the actual situation in Korea, since it was obtained from US EPA. Therefore, to more accurately estimate the pollutants present in the air, a pollution profile for Korea should be produced.
Kim, Seog-Young,Jung, Jin Hwa,Lee, Haeng Jung,Soh, Hyunsu,Lee, Sang Ju,Oh, Seung Jun,Chae, Sun Young,Lee, Jai Hyuen,Lee, Seung Jin,Hong, Yong Sang,Kim, Tae Won,Moon, Dae Hyuk American Association for Cancer Research 2017 Cancer research Vol.77 No.24
<P>These findings suggest that any inhibitor with a primary target mechanism of thymidylate synthase inhibition may be combined with trifluridine/tipiracil in colon cancer and possibly other cancer types.</P><P>In cancer therapy, enhanced thymidine uptake by the salvage pathway can bypass dTMP depletion, thereby conferring resistance to thymidylate synthase inhibition. We investigated whether sequential combination therapy of capecitabine and trifluridine/tipiracil (TAS-102) could synergistically enhance antitumor efficacy in colon cancer xenograft models. We also examined 3'-deoxy-3′-[<SUP>18</SUP>F]fluorothymidine ([<SUP>18</SUP>F]FLT) PET as a means to predict therapeutic response to a sequential combination of capecitabine and trifluridine/tipiracil. [<SUP>3</SUP>H]FLT uptake after 5-fluorouracil treatment <I>in vitro</I> and [<SUP>18</SUP>F]FLT uptake after capecitabine (360 mg/kg/day) in athymic nude mice (Balb/c-nu) with xenografts (<I>n</I> = 10–12 per group) were measured using eight human colon cancer cell lines. We determined the synergistic effects of sequential combinations of 5-fluorouracil and trifluridine <I>in vitro</I> as well as the sequential combination of oral capecitabine (30–360 mg/kg) and trifluridine/tipiracil (trifluridine 75 or 150 mg/kg with tipiracil) in six xenograft models (<I>n</I> = 6–10 per group). We observed significant increases in [<SUP>3</SUP>H]FLT uptake in all cell lines and [<SUP>18</SUP>F]FLT uptake in five xenograft models after 5-fluorouracil and capecitabine treatment, respectively. Increased [<SUP>18</SUP>F]FLT uptake after capecitabine followed by extinction of uptake correlated strongly with tumor growth inhibition (<I>ρ</I> = −0.81, <I>P</I> = 0.02). The effects of these combinations were synergistic <I>in vitro</I>. A synergy for sequential capecitabine and trifluridine/tipiracil was found only in mouse xenograft models showing increased [<SUP>18</SUP>F]FLT uptake after capecitabine. Our results suggest that the sequential combination of capecitabine and trifluridine/tipiracil is synergistic in tumors with an activated salvage pathway after capecitabine treatment in mice, and [<SUP>18</SUP>F]FLT PET imaging may predict the response to capecitabine and the synergistic antitumor efficacy of a sequential combination of capecitabine and trifluridine/tipiracil. <I>Cancer Res; 77(24); 7120–30. ©2017 AACR</I>.</P>