Mohapatra Rashmi, Ramesh Arabandir, Jayaraman Gopalsamy, Santhiya Sathiyavedu Thyagarajan, Gopinath Puthiya Mundayat
Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, India.
J Cancer Res Ther. 2009 Sep;5 Suppl 1:S53-6. doi: 10.4103/0973-1482.55144.
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.
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.
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.
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%.
2-DG effectively reduces the MMC-and 4-NQO-induced genotoxicity.
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。
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。
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。
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%。
2-DG可有效降低MMC和4-NQO诱导的遗传毒性。