Optimizing radiation therapy of brain tumours by combination of 5-bromo-2-deoxy-uridine & 2-deoxy-D-glucose.

The effects of 5-bromo-2-deoxy-uridine (BrdU) and 2-deoxy-D-glucose (2-DG) on 60Co-gamma ray induced damage were studied in a human glioma cell line grown as monolayer. Radiation induced micronuclei formation was used as an index of cytogenetic damage. Exponentially growing cells (doubling time 16-20 h) were incubated in the presence of BrdU (0.8 microM, in dark) for 24 h. After removing BrdU, cells were irradiated (1-4 Gy), incubated with or without 2-DG (2-3 h), and grown further (for 18, 24, 30 or 45 h) for assay of damage. It was observed that (i) BrdU and 2-DG treatments did not induce micronuclei formation in unirradiated cultures; (ii) pre-irradiation presence of BrdU increased the gamma-ray induced micronuclei formation; (iii) incubation of irradiated cells under sub-optimal growth conditions [Dulbecco's modified minimal essential medium (DMEM) + 1% serum, or DMEM alone] instead of growth medium (DMEM + 5% serum) progressively decreased micronuclei formation; and (iv) post-irradiation presence of 2-DG (1.25, 2.5, 5 mM, 2-3 h in DMEM + 1% serum) enhanced the radiation damage with and without BrdU treatment at all the time points studied. These observations suggest that (i) radiation induced lesions leading to micronuclei formation in proliferating cells are, at least, partly repairable; (ii) the presence of 2-DG (2DG/glucose > or = 0.25) for short intervals (approximately 2 h), could enhance radiation damage in proliferating brain tumour cells, in the absence as well as presence of BrdU incorporation; and (iii) the combination of 2-DG could reduce BrdU doses required for radiosensitization of brain tumours, reducing, thereby, its toxic side effects.

In vitro radiation responses of human intracranial meningiomas & their modifications by 2-deoxy-D-glucose.

Radiation responses of 16 human intracranial meningiomas [hemangiopericyte, 4; fibrous, 4; transitional, 4; vascular, 3; and meningiothelial, 1] and their modifications by 2-deoxy-D-glucose (2-DG) have been studied in vitro using organ cultures derived from post-operative tumour specimens. Treatment induced cytogenetic damage viz., micronuclei formation and DNA content dispersion, were analysed as indices of the radiation damage. Results showed that the 60Co gamma ray induced micronuclei frequencies in meningiomas varied over a large range (0.7-6.2%). Presence of 2-DG (at equimolar concentration with glucose) for 4 h after irradiation, increased the radiation damage by a factor of up to 2.8 in nearly 70 per cent of the cases, although a decrease was observed in 20 per cent cases. These observations can be explained on the basis of the energy linked modulations of the competitive processes of repair and fixation of radiation induced DNA lesions. The results of the study suggest that the therapy of meningiomas could be improved by combining radiotherapy with administration of 2-DG.