© Kamla-Raj 2006 Int J Hum Genet, 6(2): 133-138 (2006) Protective Effect of 2-Deoxy-D-Glucose on Chemotherapeutic Drugs Induced Damages on Peripheral Blood Lymphocytes Exposed in-Vitro P. Venkatachalam, V.R. Jayanth, Solomon F. D. Paul and V. Vettriselvi Department of Human Genetics, Sri Ramachandra Medical College & Research Institute (Deemed University), Porur, Chennai 600 116, Tamil Nadu, India KEYWORDS Bleomycin; Mitomycin-C; chromosomal aberrations; sister chromatid exchanges ABSTRACT The effect of 2-deoxy-D-glucose (2-DG), an antimetabolite of glucose was studied in peripheral blood lymphocytes (PBL) exposed to radiomimetic drug bleomycin and an alkylating agent mitomycin-C. The PBL were exposed to 2-DG (5 mM), 30 minutes pretreatment and with Bleomycin (10 to 80 μg/ml) and Mitomycin-C (2 to12 μg/ml) for three hours. The drug as well as 2-DG was removed by washing the cells with HBSS buffer. Then the cells were cultured for 48 hours to study chromosomal aberrations (CA), Translocations (TL) and 72 hours for micronuclei (MN) and Sister Chromatid Exchanges (SCE). Exposures of PBL to Bleomycin and Mitomycin-C showed, a concentration dependent increase in the aberration frequencies, both in the presence and absence of 2-DG. While, the regression analysis showed, that the presence of 2-DG reduced bleomycin induced TL, CA frequencies and Mitomycin- C induced CA and MN frequencies significantly (P<0.001) when compared to PBL treated with the drugs alone, Bleomycin induced MN frequencies and Mitomycin-C induced SCE’s reduction were not significant. The difference could be attributed to the mechanism of the action of drugs on the cells. Furthermore the alteration in the cell cycle kinetics, suggest that the presence of 2-DG during drug exposure, alter the cellular environment and delay the cell proliferation and provide sufficient time to repair the damages, could resulted in the reduced aberration frequencies. Corresponding Author: Dr P. Venkatachalam Department of Human Genetics, Sri Ramachandra Medical College & Research Institute (Deemed University), Porur, Chennai 600 116, Tamil Nadu, India Fax: 91+ 044-4767008, E-mail: venkip@yahoo.com INTRODUCTION It is well known that most of the radiation used for therapy not only controls the division of tumor cells but also mutagenic to normal cells during multiple cycles of treatment (Bleehen et al. 1974). Therefore, studies were reported on the radio protective effect of compounds like 2- Deoxy-D-gluocose (2-DG), Hoechst (Denison et al. 1992) cysteine (Pattet et al. 1949), caffeine (Franchitto et al. 1998) and calcium channel blockers (Rajeeve and Kale 1995) on normal cells. Of which the protective effect of 2-DG was extensively studied in animal models (Jain et al. 1979) and in the lymphocytes of healthy individuals (Kalia et al. 1988; Prabhu et al. 2004) as well as glioma cells followed by radiation (Dwarakanath et al. 1989). In addition to radiotherapy, chemotherapy alone or in combination with radiation plays an important role to treat malignant diseases. The combined use of chemotherapy and radiotherapy, in patients may cause a degree of injury that would be clinically toxic following either therapy alone because, both may cause toxic to the same organ by different mechanisms. Furthermore, the response of cellular systems to therapeutic agents depend on its effect on DNA, types of lesions induced, capacity of the cells to repair those lesions and cell cycle kinetics (Jain et al., 1999). As our previous study had shown a protective effect of 2-DG on radiation induced chromosomal aberrations in the PBL (Prabhu et al. 2004), the present study focus on the effect of 2-DG on radiomimectic drug bleomycin and alkylating agent mitomycin-C induced damages in PBL treated in-vitro. The PBL were exposed to those drugs in the presence of 2-DG at G 0 phase of the cells, which is the normal stage of majority of the cells in the body at any given time, which enables to some extent that the overall response of tumors surrounding cell to therapeutic drugs. The 5 mM concentration of 2-DG was selected get an equimolar concentration of glucose in the normal blood samples. MATERIALS AND METHODS In-vitro Treatment of Peripheral Blood lymphocytes to Bleomycin and Mitomycin-C: About 10 ml of peripheral blood was collected in a heparinised sterile container from a healthy