Effect of low dose radiation on somatic intrachromosomal recombination in vivo and in vitro

High doses of ionizing radiation are mutagenic in a wide range of mutation assays. The majority of radiation exposure studies in in vivo mouse mutation assays have been performed at high doses, eg greater than 1 Gy. However, these doses are not relevant to the low doses of ionizing radiation that the majority of the population might be likely to come in contact with. All radiation protection levels are based on a simple linear no threshold model which suggests that any radiation above zero is potentially harmful. The pKZ1 somatic intrachromosomal recombination (SICR) mutagenesis mouse model has proven to be a sensitive assay for low doses of chemical agents. Cells which have undergone SICR inversion events within the transgene in pKZ1 mice are scored by histochemical staining of tissue sections. We exposed pKZ1 mice to X-radiation doses ranging from 0.001 to 2 Gy. A significant increase in SICR was observed in spleen at the two highest doses of 0.1 and 2 Gy and a significant reduction in SICR below endogenous frequency was observed at the two lowest doses of 0.01 and 0.001 Gy. When a pKZ1 cell line was exposed to the same dose range, a similar J curve response was observed but with a shift to the left - with significant increases in SICR observed at the 3 highest doses and a significant decrease below endogenous frequency at the lowest dose (0.001 Gy). The next experiments will be to determine the radiation dose where the SICR frequency returns to the endogenous level. The important question posed by these results is "Is a reduction below endogenous SICR level caused by low doses of ionizing radiation anti-mutagenic?" Studies now need to be performed to investigate the effect of low doses of radiation on other mutation end-points, and the mechanism for the reduction in SICR.