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2-脱氧-D-葡萄糖对丝裂霉素C和4-硝基喹啉-1-氧化物诱导的瑞士白化小鼠体内遗传毒性的调节作用。

Modulatory action of 2-deoxy-D-glucose on mitomycin C-and 4-nitroquinoline-1-oxide-induced genotoxicity in Swiss albino mice in vivo.

作者信息

Mohapatra Rashmi, Ramesh Arabandir, Jayaraman Gopalsamy, Santhiya Sathiyavedu Thyagarajan, Gopinath Puthiya Mundayat

机构信息

Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, India.

出版信息

J Cancer Res Ther. 2009 Sep;5 Suppl 1:S53-6. doi: 10.4103/0973-1482.55144.

Abstract

BACKGROUND

2-Deoxy-D-glucose (2-DG), a structural analog of glucose is an effective inhibitor of glucose metabolism and ATP production. It selectively accumulates in cancer cells and interferes with glycolysis leading to cell death. 2-DG is shown to differentially enhance the radiation-induced damage in cancer cells both under euoxic and hypoxic conditions. A combination of 2-DG and ionizing radiation selectively destroys tumors while protecting the normal tissue. 2-DG is being advocated as an adjuvant in the radiotherapy and chemotherapy of cancer.

OBJECTIVE

The present investigation focuses on the modulatory effect of 2-DG on mitomycin C- (MMC) and 4-nitroquinoline-1-oxide (4-NQO)-induced cytogenetic damage in bone marrow cells of Swiss albino mice in vivo.

MATERIALS AND METHODS

Experimental animals were pretreated with 2-DG (500 mg/kg, i.p.) for five consecutive days followed by MMC (2 mg/kg, i.p) or 4-NQO (15 mg/kg, i.p.), 24 h prior to sacrifice. Control animals were given either the mixture of olive oil and acetone (3:1) or distilled water. Bone marrow cells were processed for the micronucleus assay and metaphase analysis for estimating cytogenetic damage.

RESULTS

2-DG significantly (P < 0.001) reduced the frequency of aberrant cells induced by MMC (approximately 90%) and 4-NQO (approximately 74%). Incidence of micronucleated polychromatic erythrocytes (MnPCEs) induced by the mutagens were reduced up to 68%.

CONCLUSION

2-DG effectively reduces the MMC-and 4-NQO-induced genotoxicity.

摘要

背景

2-脱氧-D-葡萄糖(2-DG)是葡萄糖的结构类似物,是一种有效的葡萄糖代谢和ATP生成抑制剂。它选择性地在癌细胞中蓄积,并干扰糖酵解,导致细胞死亡。研究表明,在常氧和低氧条件下,2-DG均可不同程度地增强辐射对癌细胞的损伤作用。2-DG与电离辐射联合应用可选择性地破坏肿瘤,同时保护正常组织。2-DG被推荐作为癌症放疗和化疗的辅助药物。

目的

本研究着重探讨2-DG对丝裂霉素C(MMC)和4-硝基喹啉-1-氧化物(4-NQO)诱导的瑞士白化小鼠骨髓细胞体内细胞遗传损伤的调节作用。

材料与方法

实验动物连续5天腹腔注射2-DG(500 mg/kg)预处理,于处死前24小时腹腔注射MMC(2 mg/kg)或4-NQO(15 mg/kg)。对照动物给予橄榄油和丙酮的混合物(3:1)或蒸馏水。对骨髓细胞进行微核试验和中期分析,以评估细胞遗传损伤。

结果

2-DG显著(P < 0.001)降低了MMC(约90%)和4-NQO(约74%)诱导的异常细胞频率。诱变剂诱导的微核多染红细胞(MnPCEs)发生率降低了68%。

结论

2-DG可有效降低MMC和4-NQO诱导的遗传毒性。

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