Urinary 8-hydroxy-2 -deoxyguanosine(8-OHdG) is an excellent marker of oxidative DNA damage.In this study,employing guanosine as dummy template a novel molecularly imprinted(MIP) monolithic capillary column had been sy...Urinary 8-hydroxy-2 -deoxyguanosine(8-OHdG) is an excellent marker of oxidative DNA damage.In this study,employing guanosine as dummy template a novel molecularly imprinted(MIP) monolithic capillary column had been synthesized,and that was used as medium of in-tube solid phase microextraction(SPME).Coupled with capillary electrophoresis-electrochemical detection(CE-ECD),the system of extraction and detection of 8-OHdG in urinary sample had been developed.Because of its greater phase ratio combined with conv...展开更多
Reactive oxygen species may be involved in the progression of gastric carcinomas. To clarify whether the pathology of gastric carcinoma are related to oxidative DNA damage, the expression of 8-hydroxy-2＇-deoxyguanosi...Reactive oxygen species may be involved in the progression of gastric carcinomas. To clarify whether the pathology of gastric carcinoma are related to oxidative DNA damage, the expression of 8-hydroxy-2＇-deoxyguanosine （8-OHdG） was examined in 30 patients with gastric carcinomas. Methods： The expression of 8-OHdG and apoptosis in the gastric carcinoma were measured using the methods of immunocytochemistry and deoxynucleartididyl transferase-mediated dUTP-biotin nick end labeling （TUNEL）, respectively. Results： Of the 30 cases, 25（83%） showed stronger immunoreactivity than normal control. The patients with poorly differentiated gastric carcinoma had a larger tumor size and higher labeling indices of TUNEL- and 8-OHdG-positive cells than those with well and moderately differentiated gastric carcinoma. Conclusion： Our findings suggest that oxidative DNA damage is increased in association with necroinflammation in chronic gastric injuries and determination of 8-OHdG is useful in assessing high-grade malignancy in gastric carcinomas.展开更多
An efficient and novel method for synthesizing 3′,5′-dithio-2′-deoxyguanosine was described.In this method normal guanosine was used as the starting material.A very efficient procedure was used to synthesize 2-O-to...An efficient and novel method for synthesizing 3′,5′-dithio-2′-deoxyguanosine was described.In this method normal guanosine was used as the starting material.A very efficient procedure was used to synthesize 2-O-tosylguanosine 1,which used 0.1 eq.DBTO instead of 2 eq.1 was treated with LTBH to give 9-(2-deoxy-β-D-threo-pentofuranosyl)guanine 2.2 could be easily turned to the target compound.展开更多
8-Oxoguanine （8-oxoG）, a critical mutagenic DNA lesion induced by reactive oxy- gen species, gives rise to a G·C→T·A transversion during replication and thereby must be repaired. The effects of explicit a...8-Oxoguanine （8-oxoG）, a critical mutagenic DNA lesion induced by reactive oxy- gen species, gives rise to a G·C→T·A transversion during replication and thereby must be repaired. The effects of explicit and implicit solvent molecules on the hydrolysis cleavage of N-Glycosidic bond in 8-oxo-7,8-dihydro-2＇-deoxyguanosine （8-oxo-dG） have been systematically clarified in the present work based upon two types of computational models. Detailed potential energy surface （PES） scans and full unconstraint optimizations for all the representative points on PESs were carried out at the B3LYP/6-31＋G（d） level of theory. The effect of implicit solvent was tested by single-point calculation at the SCRF/IEF-PCM model. The results illustrate that the direct hydrolysis model involving one explicit water molecule can’t provide a complete depiction of the hydrolysis process of 8-oxo-dG, attributed to the insufficiency of nucleophile activation and leaving group stabilization. The expansion hydrolysis model involving four explicit water molecules, however, facilitates discrete proton transfer and therefore produces smooth reaction surfaces for both the dissociative （SN1） and concerted （SN2） pathways. The presence of the implicit solvent substantially lowers all activation energies and the SN1 process is more favorable than the SN2 process. The data and insights present here agree well with the experimental results and have given out a baseline for the enzymatic deglycosylation reaction of 8-oxo-dG.展开更多
基金the support of the National Natural Science Foundation of China(No.20575051).
文摘Urinary 8-hydroxy-2 -deoxyguanosine(8-OHdG) is an excellent marker of oxidative DNA damage.In this study,employing guanosine as dummy template a novel molecularly imprinted(MIP) monolithic capillary column had been synthesized,and that was used as medium of in-tube solid phase microextraction(SPME).Coupled with capillary electrophoresis-electrochemical detection(CE-ECD),the system of extraction and detection of 8-OHdG in urinary sample had been developed.Because of its greater phase ratio combined with conv...
基金Nature Science Fundation of Jiangsu Province (BK2004146)Science Fund of Department of Education of Jiangsu Province (03KJB310085)
文摘Reactive oxygen species may be involved in the progression of gastric carcinomas. To clarify whether the pathology of gastric carcinoma are related to oxidative DNA damage, the expression of 8-hydroxy-2＇-deoxyguanosine （8-OHdG） was examined in 30 patients with gastric carcinomas. Methods： The expression of 8-OHdG and apoptosis in the gastric carcinoma were measured using the methods of immunocytochemistry and deoxynucleartididyl transferase-mediated dUTP-biotin nick end labeling （TUNEL）, respectively. Results： Of the 30 cases, 25（83%） showed stronger immunoreactivity than normal control. The patients with poorly differentiated gastric carcinoma had a larger tumor size and higher labeling indices of TUNEL- and 8-OHdG-positive cells than those with well and moderately differentiated gastric carcinoma. Conclusion： Our findings suggest that oxidative DNA damage is increased in association with necroinflammation in chronic gastric injuries and determination of 8-OHdG is useful in assessing high-grade malignancy in gastric carcinomas.
基金supported by the National Natural Science Foundation of China(No.20872078)the Basic Science Research Foundation of Tsinghua University(No.JC 2001046)
文摘An efficient and novel method for synthesizing 3′,5′-dithio-2′-deoxyguanosine was described.In this method normal guanosine was used as the starting material.A very efficient procedure was used to synthesize 2-O-tosylguanosine 1,which used 0.1 eq.DBTO instead of 2 eq.1 was treated with LTBH to give 9-(2-deoxy-β-D-threo-pentofuranosyl)guanine 2.2 could be easily turned to the target compound.
基金supported by the National Natural Science Foundation of China(21203153 and 21173151)Science&Technology Department(2011JY0136)+1 种基金Department of Education(12ZA174)of Sichuan ProvinceChina West Normal University(11B002)
文摘8-Oxoguanine （8-oxoG）, a critical mutagenic DNA lesion induced by reactive oxy- gen species, gives rise to a G·C→T·A transversion during replication and thereby must be repaired. The effects of explicit and implicit solvent molecules on the hydrolysis cleavage of N-Glycosidic bond in 8-oxo-7,8-dihydro-2＇-deoxyguanosine （8-oxo-dG） have been systematically clarified in the present work based upon two types of computational models. Detailed potential energy surface （PES） scans and full unconstraint optimizations for all the representative points on PESs were carried out at the B3LYP/6-31＋G（d） level of theory. The effect of implicit solvent was tested by single-point calculation at the SCRF/IEF-PCM model. The results illustrate that the direct hydrolysis model involving one explicit water molecule can’t provide a complete depiction of the hydrolysis process of 8-oxo-dG, attributed to the insufficiency of nucleophile activation and leaving group stabilization. The expansion hydrolysis model involving four explicit water molecules, however, facilitates discrete proton transfer and therefore produces smooth reaction surfaces for both the dissociative （SN1） and concerted （SN2） pathways. The presence of the implicit solvent substantially lowers all activation energies and the SN1 process is more favorable than the SN2 process. The data and insights present here agree well with the experimental results and have given out a baseline for the enzymatic deglycosylation reaction of 8-oxo-dG.
文摘目的：观察2-脱氧-D-葡萄糖（2-DG）联合紫杉醇（Taxol）对C3H小鼠乳腺癌移植瘤的抑制作用及其机制。方法建立肿瘤模型，待肿瘤体积达到100~300 mm3后，随机分为4组：对照组，2-DG组，Taxol组及2-DG和Taxol联用组。腹腔注射给药治疗18 d并观察记录肿瘤体积，每3 d 1次，绘制肿瘤生长曲线。接种后第19天处死动物，称量肿瘤质量，使用原位凋亡检测法（TUNEL）检测2-DG联合Taxol对肿瘤细胞凋亡的影响，免疫组化法检测血管内皮生长因子（VEGF）的表达。结果2-DG和Taxol联用组可明显抑制肿瘤生长（P〈0.05），单用Taxol组抑瘤率为36.97%，联用组为66.06%。TUNEL结果显示2-DG和Taxol联用组肿瘤组织中出现大量蓝黑色凋亡细胞，明显多于对照组，2-DG组与Taxol组，且VEGF的表达明显降低。结论2-DG联合Taxol对C3H小鼠移植性乳腺癌生长具有明显的抑制作用，这可能与诱导肿瘤细胞凋亡及抑制VEGF表达有关。
