Sensitive detection of somatic intrachromosomal recombination in response to low dose radiation exposure: how low can we go?

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    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. Radiation protection levels have been based on a simple linear no threshold model, which suggests that any radiation above zero is potentially harmful. We utilised the sensitive pKZ1 somatic intrachromosomal recombination (SICR) mutagenesis mouse model to study the mutagenic effect of very low doses of X-radiation. Cells which have undergone SICR inversion events within the transgene in pKZ1 mice are scored by histochemical staining of E.coli -galactosidase in tissue sections. pKZ1 mice were subjected to a single whole-body, high dose-rate, X-radiation exposure ranging from 1 Gy up to 2 Gy. A non-linear dose-response was observed using SICR in spleen tissue as the end-point with significant inductions in SICR at higher doses and a significant reduction in SICR below endogenous frequency at lower doses. A similar dose response was observed when a pKZ1 cell line was exposed to the same dose range. Preliminary results from adaptive response experiments, low dose-rate experiments, and the effect of a defective atm gene using pKZ1 mice will also be discussed. The important question posed by these results is "Is a reduction below endogenous SICR level caused by low doses of ionizing radiation anti-mutagenic?" This question will be discussed in terms of possible mechanisms. Research funded by the Low Dose Radiation Research Program, Biological and Environmental Research (BER), U.S. Department of Energy, grant # DE-FG02-01ER63227.
    Original languageEnglish
    Number of pages1
    Publication statusPublished - 2003
    Event12th International Congress of Radiation Research - Brisbane Convention and Exhibition Centre, Brisbane, Australia
    Duration: 17 Aug 200322 Aug 2003
    Conference number: 12


    Conference12th International Congress of Radiation Research
    Abbreviated titleICRR 2003


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