量研学術機関リポジトリ「QST-Repository」は、国立研究開発法人 量子科学技術研究開発機構に所属する職員等が生み出した学術成果（学会誌発表論文、学会発表、研究開発報告書、特許等）を集積しインターネット上で広く公開するサービスです。 Welcome to QST-Repository where we accumulates and discloses the academic research results(Journal Publications, Conference presentation, Research and Development Report, Patent, etc.) of the members of National Institutes for Quantum and Radiological Science and Technology.
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In contradiction to classical paradigm, which assumes that radiation effects
are directly proportional to energy deposit, numerous in vitro, in vivo and
in utero studies, including ours, described the existence in various models
of a radiation-induced adaptive response (AR), according to which
pre-exposure to low priming dose of ionizing radiations decreases the
biological effects of a subsequent higher challenging dose. Several of our
AR experimental models will be introduced in this presentation.
We demonstrated the existence of AR in mice during late organogenesis.
Molecular mechanisms underlying AR in this model were investigated. Using
DNA microarrays and real-time quantitative fluorescence RT-PCR, AR-specific
gene modulations were identified. Our results suggested the involvement of
signal transduction and p53-related pathways in the induction of AR, in
agreement with previous investigations showing that AR could be dependent on
p53 activity. The observed gene modulations may also have possible
consequences for subsequent developmental process of the fetus. This is the
first report of AR-specific modulations at the molecular level in utero,
which could serve as a basis for subsequent studies aimed at understanding
AR in this model and possible long term effects. In addition, analysis of
p53 protein levels in adapted murine fetal limb bud cells cultured in vitro
will be presented and the involvement of p53 in AR will be discussed.
We also focused our interest on the possibility of observing an AR when
using high-LET radiation. Knowing that high-LET heavy-ion radiations
produce non-randomly distributed DNA damage in the form of clusters, or
locally multiply damaged sites (LMDS), we tried to investigate whether this
kind of damage can trigger an AR specific DNA repair, and whether AR
could protect against LMDS induction by challenging radiations. Biological
effects of low and high-LET irradiation (performed at HIMAC, Chiba) were
studied in vitro in cultured lymphoblastoid cell lines, which were exposed
to priming and/or challenging radiation (either X-Rays or accelerated
heavy-ions at various LETs). Our results demonstrated the existence of a
mutagenic AR in this model, and pointed to a possible involvement of DSB
repair mechanisms. The ability of high LET heavy-ion radiation (at low dose
and low dose-rate) to induce AR is under investigation. Some perspectives
for this study will also be discussed.
Radiation-induced Adaptive Response: in vitro and in utero Studies
