SREL Reprint #2531

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

J. A. Kind1, R. N. Winn2, M. E. T. I. Boerrigter3, C. H. Jagoe4, T. C. Glenn4, and C. E. Dallas5

1Terra, Inc., Tallahassee, Florida, USA
2School of Forest Resources, University of Georgia, Athens, Georgia, USA
3Leven, Inc., Bogart, Georgia, USA
4Savannah River Ecology Laboratory, University of Georgia, Aiken, South Carolina, USA
5Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia,
Athens, Georgia, USA

Abstract: The radioadaptive response where a small priming dose of ionizing radiation can lessen the effects of subsequent exposure to a higher radiation challenge dose, was investigated in brain and liver within transgenic mice. Although it is well characterized in models in vitro, current radioadaptive response research has focused on particular cell types (i.e., lymphocytes) and does not provide comparative data for responses of multiple tissues within an organism. Transgenic animals are useful for such comparisons, because the transgene is integrated into all cells in the body. The pUR288 lacZ plasmid-based transgenic mouse model utilizes a plasmid vector allowing highly efficient recovery of mutalional targets, including large size-change mutations that result from radiation exposure. Female C57Bl/6 pUR288 lacZ mice were 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. Spontaneous mutant frequencies in lacZ were significantly higher in liver than in 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 the brain. Restriction enzyme analysis of rescued mutant plasmids revealed a decrease in large size-change mutations at the three priming doses in brain. This study demonstrates the utility of this model for the investigation of radiological processes of large size-change mutations, as well as showing a radioadaptive response in brain, but not liver, of mice in vivo.

SREL Reprint 2531

Kind, J. A., R. N. Winn, M. E. T. I. Boerrigter, C. H. Jagoe, T. C. Glenn, and C. E. Dallas. 2001. Investigation of the radioadaptive response in brain and liver of pUR288 lacZ transgenic mice. Journal of Toxicology and Environmental Health 63:207-220.

This information was provided by the University of Georgia's Savannah River Ecology Laboratory (srel.uga.edu).