Pre-exposure to low doses: modulation of frequencies and repair of x-ray induced DNA damage?

Full text: Ionizing radiation (IR) interacts with DNA either by direct hit, or by the production of reactive oxygen inducing strand breaks and base modifications. There is much evidence indicating alleviation of biological effects after pre-exposure to low doses of IR. The mechanisms of this so called adaptive response have not yet been elucidated. Low dose exposure might reduce damage induction from the high dose, or might induce repair mechanisms. The aim of this study was to test whether low radiation doses can cause protection against high dose effects by modulation of initial damage and repair. By using confluent (G1 phase) human primary fibroblasts, we ruled out possible effects of the conditioning dose on the cell cycle. When cells were pre-exposed to 0.05 Gy X-rays 4 hours prior to challenging dose (0-6 Gy), no protective effect was observed against damage induction, measured by comet assay. However, pre-exposure to 0.1 Gy gave slightly lower tail moments in cells challenged with 6 Gy. No difference was observed in repair kinetics between conditioned and unconditioned cells. The results were very similar for 3 different human fibroblast cell lines. DNA DSB were detected even after low doses with gamma H2AX fluorescence. A linear dose response relationship was found in the dose range 0-3 Gy. In 3 out of 4 experiments, the amount of DSB measured by total nucleus fluorescence was lower in 0.05 Gy conditioned than in unconditioned cells. No difference in repair kinetics between conditioned and unconditioned cells was observed. Taken together, our results indicate that the modulation of DNA damage and repair by pre-exposure to low doses is either low or absent. These and other data (Laval, 1988) (Bravard et al, 1999) suggest that the induction of anti-oxidant activity may be dependent on the pre-exposure agent and that for repair, the occurrence of an adaptive response, may be dependent on the type of lesion to be repaired (Weinfeld et al, 2001)