Effect of lactate on the recovery of CHO-KI cells from gamma radiation damage

The effect of pre-exposure of CHO-KI cells to lactate on their capacity to recover from or repair radiation damage was examined. Prolonged pre-exposure to lactate and a number of inhibitors of glycolysis has previously been shown to reduce the cell survival after irradiation. Following a split dose of irradiation, cells pre-treated with lactate for 18 hours had a higher relative recovery factor than controls even though survival following a single dose was reduced. Where lactate was added just before irradiation it had a radiation protective effect on the single dose survival curve and no effect on recovery. To investigate a possible involvement of NADH generation via lactate dehydrogenase in the mechanism, oxamate, a non-metabolisable analogue of lactate, was investigated. It reduced the survival of irradiated CHO-KI cells following prolonged and short pre-exposure and did not significantly affect the recovery factor. It is suggested that since lactate and oxamate both inhibit glucose breakdown, their radiobiologic effects may be due to depletion of cellular energy substrates necessary for repair. In contrast, the increased recovery and short term radiation protective effect seen with lactate only may involve LDH activity. (orig.)