Modification of radiation damage in transformed mammalian cells by 5-bromo-2-deoxy-uridine and 2-deoxy-D-glucose.

ABSTRACT

The effects of 2-deoxy-D-glucose (2-DG) and 5-bromo-2-deoxy-uridine (BrdU) on gamma ray (60Co) induced damage were studied in monolayer cultures of transformed mammalian (BHK-21) cells. Micronuclei formation and changes in DNA content dispersion were used as indices of cytogenetic damage. Exposure of cells to BrdU (0.8 microM) for nearly two cell cycles before irradiation significantly increased micronuclei formation in exponentially growing cells. Incubation of irradiated cells under suboptimal growth conditions (in HBSS) for 4 hr, instead of growth medium, decreased the manifestation of damage. However, post-irradiation presence of 2-DG (5 mM, equimolar with glucose; 4 hr) in growth medium or HBSS significantly increased radiation damage. The effects of 2-DG treatment following irradiation in plateau phase were quantitatively less. These results suggest that (i) radiation induced DNA lesions leading to micronuclei formation in BrdU incorporated cells are partly repairable; (ii) 2-DG could increase radiation induced cytogenetic damage in transformed mammalian cells, possibly by inhibiting the cellular repair processes; and (iii) combination of 2-DG treatment may decrease the BrdU doses required for radiosensitization of proliferating tumour cell populations.