Effect of low dose radiation on somatic intrachromosomal recombination in vivo and in vitro

Pamela Sykes, Madhava Bhat, John Cormack, Alexander Morley, Antony Hooker

    Research output: Contribution to conferenceAbstract

    Abstract

    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. All radiation protection levels are based on a simple linear no threshold model which suggests that any radiation above zero is potentially harmful. The pKZ1 somatic intrachromosomal recombination (SICR) mutagenesis mouse model has proven to be a sensitive assay for low doses of chemical agents. Cells which have undergone SICR inversion events within the transgene in pKZ1 mice are scored by histochemical staining of tissue sections. We exposed pKZ1 mice to X-radiation doses ranging from 0.001 to 2 Gy. A significant increase in SICR was observed in spleen at the two highest doses of 0.1 and 2 Gy and a significant reduction in SICR below endogenous frequency was observed at the two lowest doses of 0.01 and 0.001 Gy. When a pKZ1 cell line was exposed to the same dose range, a similar J curve response was observed but with a shift to the left - with significant increases in SICR observed at the 3 highest doses and a significant decrease below endogenous frequency at the lowest dose (0.001 Gy). The next experiments will be to determine the radiation dose where the SICR frequency returns to the endogenous level. The important question posed by these results is "Is a reduction below endogenous SICR level caused by low doses of ionizing radiation anti-mutagenic?" Studies now need to be performed to investigate the effect of low doses of radiation on other mutation end-points, and the mechanism for the reduction in SICR.
    Original languageEnglish
    Number of pages1
    Publication statusPublished - 2003
    EventEnvironmental Mutagenesis: From Mechanisms to Risk Assessment - Fontainbleau Hilton Resort, Miami Beach, United States
    Duration: 10 May 200314 May 2003
    Conference number: 34th
    https://www.emgs-us.org/d/do/1748 (Conference program)

    Conference

    ConferenceEnvironmental Mutagenesis
    Abbreviated titleEMGS 2003
    CountryUnited States
    CityMiami Beach
    Period10/05/0314/05/03
    Internet address

    Keywords

    • ionizing radiation
    • somatic intrachromosomal recombination
    • mutation assays
    • radiation exposure
    • in vivo mouse mutation

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    Sykes, P., Bhat, M., Cormack, J., Morley, A., & Hooker, A. (2003). Effect of low dose radiation on somatic intrachromosomal recombination in vivo and in vitro. Abstract from Environmental Mutagenesis, Miami Beach, United States.