Characterisation of an adaptive response in pKZ1 mice after exposure to X-radiation

Currently, little is known about the mutagenic effects of exposure to low doses of ionising radiation because of the relatively insensitive end-points used for mutation detection. The pKZ1 mouse mutation assay enables detection of somatic intrachromosomal recombination (SICR) as a mutation end-point. We have previously observed an increase in SICR in spleen in response to a single dose of X-radiation at doses above 0.1 Gy, and a decrease in SICR below endogenous frequency after a single dose of X-radiation between 0.01 – 0.001 Gy. These doses are 2-3 orders of magnitude lower than previously reported with other mutagenicity assays.

The aim of the present study is to utilize the sensitivity of the pKZ1 model to determine if low doses of X-radiation can reduce SICR induced by a subsequent high dose of X-radiation (i.e. an adaptive response). We have performed experiments in pKZ1 mice with a priming dose of 0.01 Gy, followed 4 hours later with a challenge dose of 1 Gy. We observed a decrease in induced SICR in the animals that had been treated with the low priming dose prior to receiving 1 Gy, compared to the animals that received 1 Gy alone. These data demonstrate that the pKZ1 model can be used to study adaptive response to X-radiation.

The next adaptive response experiments using the pKZ1 model will be to determine the lowest priming dose and lowest test dose capable of inducing an adaptive response. These studies will have important implications for the way we view the risk of exposure to low doses of X-radiation in the environment and potentially the way medical practice utilises X-radiation for diagnosis and treatment.