Investigation of the radioadaptive response in brain and liver of pUR288 lacZ transgenic mice

The radioadaptive response, where a small priming dose of ionizing radiatio n can lessen the effects of subsequent exposure to a higher radiation chall enge dose, was investigated in brain and liver within transgenic mice. Alth ough it is well characterized in models in vitro, current radioadaptive res ponse research has focused on particular cell types (i.e., lymphocytes) and does nor provide comparative data for responses of multiple tissues within an organism. Transgenic animals are useful for such comparisons, because t he transgene is integrated into ail cells in the body. The pUR288 lacZ plas mid-based transgenic mouse model utilizes a plasmid vector allowing highly efficient recovery of mutational targets, including large size-change mutat ions that result from radiation exposure. Female C57Bl/6 pUR288 lacZ mice w ere exposed to priming doses of 0.075- to 0.375-Gy x-rays over a 3-d period . After 3 wk. they received an acute challenge dose of 2.5-Gy x-rays. Spont aneous mutant frequencies in lacZ were significantly higher in liver than i n brain (6.62 x 10(-5) vs. 3.51 x 10(-5)). in the absence of a priming dose , the 2.5-Gy challenge doubled the mutant frequency of both liver and brain (13.38 x 10(-5), and 7.63 x 10(-5) respectively). Priming doses of 0.15, 0 .225, and 0.375 Gy significantly reduced (by 40%) the mutagenic effects of the 2.5-Gy challenge in brain. Restriction enzyme analysis of rescued mutan t plasmids revealed a decrease in large size-change mutations at the three priming doses in brain. This study demonstrates the utility of this model f or the investigation of radiological processes of large size-change mutatio ns, as well as showing a radioadaptive response in brain, but not liver, of mice in vivo.