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dc.description.abstractβ-Thujaplicin is a natural monoterpenoid found in the wood of trees in the family Cupressaceae. To evaluate the effects of β-thujaplicin on the breast cancer growth, the metabolic profiling of serum, liver and urine obtained from N-methyl-N-nitrosourea-(NMU) induced rat mammary tumor model (BC), NMU-induced rat mammary tumor model received intra-abdominal dose of β-thujaplicin (B7.5) and healthy control rats (HC) were determined using a gas chromatograph coupled with time-of-flight mass spectrometer (GC-TOF-MS). In addition, western blot analysis was performed to evaluate the activity of ERα. In total, 42 metabolites, including 7 carbohydrates, 8 lipids, 9 organic acids, and 18 amino acids, were identified in serum of rats. Metabolites such as palmitic acid, linoleic acid, oleic acid and arachidonic acid were significantly decreased in BC and B7.5 groups compared to HC group. Citric acid was also increased in BC than HC group. In particular, tartaric acid was considered as a possible biomarker which could indicate metabolic change between healthy control rats and NMU-induced breast cancer rat group. In partial least-squares discriminate analysis (PLS-DA) derived score plot in serum, B7.5 group was differentiated from other groups. The main metabolites associated with the separation were glucose, tyrosine, tryptophan, ornithine, hydroxyproline and threonine in B7.5 group. On the other hand, a total of 38 and 28 metabolites were detected in liver and urine of rats, respectively. The significantly changed metabolites such as ribose, myo-inositol, palmitic acid and linoleic acid in liver indicate that metabolic change between healthy control rats and NMU-induced rat mammary tumor groups.;본 연구에서는 국내 자생 방향식물인 편백나무의 심재에 함유되어있는 성분인 β-thujaplicin이 유방암의 성장에 미치는 영향을 탐색하기 위하여 mass spectrometry (MS)를 기반으로 하는 metabolomics 연구기법을 수행하였다.또한 ERα의 활성을 측정하기 위하여 western blot이 사용되었다.N-methyl-N-nitrosourea (NMU)로 유방암이 유도된 rat 모델에 β-thujaplicin을 7.5 mg/kg body weight의 농도로 9주 동안 복강 투여하였다. 그 후 건강한 그룹, NMU로 유방암이 유도된 그룹, NMU로 유방암을 유도한 후 β-thujaplicin을 투여한 그룹들의 생체시료 (serum, liver, urine) 내의 1차 대사산물을 gas chromatography time-of-flight mass spectrometry (GC-TOF-MS)를 통해 프로파일링하였으며, 다변량 통계기법인 PLS-DA를 이용하여 그룹 내 판별 분석을 실시하였다. Target analysis 방법을 이용하여 serum 내 총 42 가지의 1차 대사산물을 동정하였으며, 7가지의 당류, 8가지의 지방류, 9가지의 유기산류, 18가지의 아미노산류가 확인되었다. Palmitic acid, linoleic acid, oleic acid 그리고 그리고 arachidonic acid 와 같은 대사산물을 통해 유방암이 유도된 그룹과 건강한 그룹 간의 대사적 변화의 차이를 확인 할 수 있었다. 특히, tartaric acid는 β-thujaplicin의 anti-cancer 효과에 의하여 유방암이 유도된 그룹과 유방암 유도 후 β-thujaplicin을 투여한 그룹 간에 대사적 변화를 보여주는 바이오 마커 (Possible biomarker)로 추정된다. 또한, western blot 수행결과 β-thujaplicin을 투여하였을 때 항암효과가 확인되었다. Serum에서 수행한 PLS-DA분석에 따르면 유방암을 유도한 그룹과 유방암 유도 후 β-thujaplicin을 투여한 그룹이 분리되는 것을 확인할 수 있었으며, 이들 그룹의 구분에 관여하는 주요 대사체는 B7.5그룹의 glucose, tyrosine, ornithine, hydroxyproline 그리고 threonine이었다. Liver와 urine에서는 각각 38개와 28개의 대사산물이 동정되었다. Liver에서는 ribose, myo-inositol, palmitic acid 그리고 linoleic acid과 같은 대사산물을 통하여 유방암이 유도된 그룹과 건강한 그룹 간의 대사적 차이를 확인할 수 있었다.-
dc.description.tableofcontents1. Introduction 1 2. Materials and methods 5 2.1. Chemicals 5 2.2. Animals 5 2.3. Tumor induction and dosing treatment of β-thujaplicin 6 2.4. Metabolic profiling using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) 8 2.4.1. Serum preparation for GC-TOF-MS analysis 8 2.4.2. Liver preparation for GC-TOF-MS analysis 9 2.4.3. Urine preparation for GC-TOF-MS analysis 10 2.4.4. Serum, liver, and urine sample analysis using GC-TOF-MS 11 2.4.5. Identification and quantification of primary metabolites in serum, liver and urine using GC-TOF-MS 12 2.5. Statistical analysis 13 3. Results and discussions 14 3.1. β-Thujaplicin effect on tumor volume, tumor weight, multiplicity and activities of ERα in breast cancer tissues 14 3.2. Metabolite profiling and possible biomarkers of serum from rat received β-thujaplicin . 17 3.2.1. Metabolite profiling by GC-TOF-MS 17 3.2.2. Partial least square discriminant analysis (PLS-DA) 27 3.3. Metabolite profiling and possible biomarkers of liver from rat received β-thujaplicin 30 3.3.1. Metabolite profiling by GC-TOF-MS 30 3.3.2. Partial least square discriminant analysis (PLS-DA) 38 3.4. Metabolite profiling and possible biomarkers of urine from rat received β-thujaplicin 41 3.4.1. Metabolite profiling by GC-TOF-MS 41 3.4.2. Partial least square discriminant analysis (PLS-DA) 45 4. Conclusion 48 References 49 Abstract (in Korean) 61-
dc.format.extent1410381 bytes-
dc.publisher이화여자대학교 대학원-
dc.titleMetabolic profiling of serum, liver and urine in N-methyl-N-nitrosourea-induced rat mammary tumor model treated with β-thujaplicin-
dc.typeMaster's Thesis-
dc.format.pagevii, 62 p.-
dc.identifier.major대학원 식품공학과- 2-
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