Lack of a low-dose radiation adaptive response on prostate cancer progression in the TRAMP model

Pamela Sykes, Rebecca Ormsby, Benjamin Blyth, Eva Bezak, Michelle Newman, Wayne Tilley, Mark Lawrence

    Research output: Contribution to journalMeeting Abstract

    26 Citations (Scopus)

    Abstract

    Current understanding of the biological mechanisms underlying the responses of prostate tissue to ionising radiation exposure, including cancer induction is surprisingly limited for both high and low dose exposures. Low dose radiation‐induced adaptive responses for increased cancer latency and decreased cancer frequency have been demonstrated in mouse animal models, largely for haematological cancers. This study is the first examination of the effects of high‐ and low‐dose whole‐body radiation exposure on prostate cancer development using an autochthonous mouse model (TRAMP, TRansgenic Adenocarcinoma of the Mouse Prostate) of prostate cancer.

    TRAMP mice were exposed to acute high (2 Gy), single low (50 mGy) and repeated (5 × 50 mGy) low doses of X‐rays to evaluate both the potential prostate cancer inducing/promoting effects of high‐dose radiation and low‐dose adaptive response phenomena. Prostate weights, histopathology, and time‐to‐palpable tumour were examined after high dose X‐rays. Proliferation (Ki‐67), apoptosis and DNA damage (gamma‐H2AX) and transgene expression (large T‐antigen) were examined within TRAMP prostate sections after high and low doses.

    Neither high‐ nor low‐dose radiation‐induced effects on prostate cancer progression were observed for any of the endpoints studied, suggesting that modulation of tumourigenesis in the TRAMP model is largely resistant to such exposures. However, further study is required to better assess the effects of radiation exposure using alternative prostate cancer models that incorporate normal prostate.

    This work was funded by the Prostate Cancer Foundation of Australia (ID: GC‐0810) and the Flinders Medical Centre Foundation.
    Original languageEnglish
    Pages (from-to)39
    Number of pages1
    JournalBritish Journal of Urology International
    Volume112
    Issue numberS1
    DOIs
    Publication statusPublished - 2013
    EventProstate Cancer World Congress & 14th Australasian Prostate Cancer Conference -
    Duration: 6 Aug 2013 → …

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