title: Temporal Responses to X-Radiation Exposure in Spleen in the pKZ1 Mouse Recombination Assay.
abstract: The in vivo mouse transgenic pKZ1 chromosomal inversion assay is a sensitive assay that responds to very low doses of DNA-damaging agents. pKZ1 inversions are measured as the frequency of cells expressing E. coli β-galactosidase protein, which can only be produced from an inverted pKZ1 transgene. In previous studies we reported that a single whole-body low dose of 0.01 mGy X rays alone caused an increase in pKZ1 chromosomal inversions in spleen when analyzed 3 days postirradiation, and yet this same dose could protect from high-dose-induced inversions when delivered as a conditioning dose 4 h before or after a 1 Gy challenge dose. In an attempt to explain these results, we performed temporal studies over a wide radiation dose range to determine if the inversion response was temporally different at different doses. pKZ1 mice were irradiated with a single whole-body X-ray dose of 0.01 mGy, 1 mGy or 1 Gy, and spleen sections were then analyzed for pKZ1 inversions at 7 h, 1 day or 7 days after exposure. No change in inversion frequency was observed at the 7 h time point at any dose. At day 1, an increase in inversions was observed in response to the 0.01 mGy dose, whereas a decrease in inversions below sham-treated frequency was observed for the 1 mGy dose. Inversion frequency for both doses returned to sham-treated inversion frequency by day 7. To our knowledge, this is the first reported study to examine the temporal nature of a radiation response spanning a wide dose range, including doses relevant to occupational exposure, and the results are dynamic and dose specific. The results suggest that inversions induced after low-dose irradiation are removed by homeostatic mechanisms within a short time frame, and underscore the importance of studying responses over a period of time when interpreting radiation effects.
authors.affiliation: a   Flinders Centre for Innovation in Cancer, Flinders University, Bedford Park, South Australia;
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Ormsby
authors.affiliation: a   Flinders Centre for Innovation in Cancer, Flinders University, Bedford Park, South Australia;
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Staudacher
authors.affiliation: a   Flinders Centre for Innovation in Cancer, Flinders University, Bedford Park, South Australia;
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Blyth
authors.affiliation: b   International Centre for Allied Health Evidence and Sansom Institute for Health Research, University of South Australia, Adelaide, Australia; and.|c   School of Physical Sciences, University of Adelaide, Adelaide, Australia.
authors.forename: Eva
authors.initials: E
authors.lastname: Bezak
authors.affiliation: a   Flinders Centre for Innovation in Cancer, Flinders University, Bedford Park, South Australia;
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Sykes
mesh_terms: D000818:Animals; D007446:Chromosome Inversion / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D013154:Spleen / Q000378:metabolism / Q000528:radiation effects*; D013997:Time Factors; D014965:X-Rays / Q000009:adverse effects; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D001616:beta-Galactosidase