Perumal Venkatachalam, Solomon Paul F D, Jayanth Vikram R
Department of Human Genetics, Sri Ramachandra Medical College & Research Institute (Deemed University), Porur, Chennai, India.
J Cancer Res Ther. 2009 Sep;5 Suppl 1:S48-52. doi: 10.4103/0973-1482.55142.
Chemotherapy is the treatment of cancer with drugs, often used as either adjuvant or neoadjuvant or in conjunction with radiation and surgery. Unfortunately, majority of the drugs are toxic to normal tissues, the toxicity being resulting from multidrug protocol used to induce remissions and achieve tumor care. While it has been demonstrated for compounds like the 2-deoxy-glucose (2-DG) used as a modulator for radiation-induced damages, such studies were rarely reported for chemotherapeutic drugs.
To study the effect of 2-DG on radiation-and chemotherapeutic drug-induced chromosomal aberrations in normal and tumor cells exposed in vitro.
The peripheral blood lymphocytes (PBLs) and BMG-1 cells were exposed to radiation and chemotherapeutic drugs (bleomycin and mitomycin-C) in the presence and absence of 2-DG. The treated cells were cultured for various durations, arrested at either metaphase or cytokinesis stage of the cell cycle. The stable and unstable aberrations were recorded using Giemsa staining and FISH technique. The cell cycle kinetics was studied using fluorescence plus Giemsa (FPG) staining.
The presence of 2-DG reduced stable and unstable chromosome aberrations (CA) significantly (P < 0.001), in PBLs induced by radiation, bleomycin and mitomycin-C, when compared to cells treated with radiation or the drugs and increased significantly in BMG cells (P < 0.001). Furthermore, the presence of 2-DG altered the cell cycle kinetics in the PBLs and BMG-1 cells. Thus the overall results showed protection effect on the normal cell damages induced by radiation and chemotherapeutic drugs, while sensitizes the tumor cell.
The obtained results suggest that 2-DG in combination with radiotherapy/chemotherapy could lead to an improvement in tumor therapy by sensitizing the tumor cells while protecting the normal cells.
化疗是使用药物治疗癌症，通常用作辅助治疗、新辅助治疗，或与放疗及手术联合使用。不幸的是，大多数药物对正常组织有毒性，这种毒性源于用于诱导缓解和实现肿瘤治疗的多药方案。虽然已证明像2-脱氧葡萄糖（2-DG）这样的化合物可作为辐射诱导损伤的调节剂，但针对化疗药物的此类研究却鲜有报道。
研究2-DG对体外暴露的正常细胞和肿瘤细胞中辐射及化疗药物诱导的染色体畸变的影响。
外周血淋巴细胞（PBLs）和BMG-1细胞在有或无2-DG的情况下暴露于辐射和化疗药物（博来霉素和丝裂霉素-C）。将处理后的细胞培养不同时长，使其停滞在细胞周期的中期或胞质分裂期。使用吉姆萨染色和荧光原位杂交（FISH）技术记录稳定和不稳定的畸变。使用荧光加吉姆萨（FPG）染色研究细胞周期动力学。
与接受辐射或药物处理的细胞相比，2-DG的存在显著降低了辐射、博来霉素和丝裂霉素-C诱导的PBLs中稳定和不稳定染色体畸变（CA）（P < 0.001），而在BMG细胞中显著增加（P < 0.001）。此外，2-DG的存在改变了PBLs和BMG-1细胞的细胞周期动力学。因此，总体结果显示对辐射和化疗药物诱导的正常细胞损伤有保护作用，同时使肿瘤细胞敏感。
所得结果表明，2-DG与放疗/化疗联合使用可通过使肿瘤细胞敏感同时保护正常细胞来改善肿瘤治疗。
