BACKGROUND 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. OBJECTIVE To study the effect of 2-DG on radiation-and chemotherapeutic drug-induced chromosomal aberrations in normal and tumor cells exposed in vitro. METHODS 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. RESULTS 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. CONCLUSIONS 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.