Cell and Tissue Signaling

Tuesday, October 18, 2005 3:00 PM-5:00 PM Exhibit Hall

(PP251) Radiation induced signalling leads to apoptotic response in transformed cells: involvement of cytokines and ROS.

Portess, Daniel *,1, Hill, Mark1, Bauer, Georg2, O'Neill, Peter1, 1 Radiation and Genome Stability Unit, Didcot, Oxfordshire, United Kingdom2 Abteilung Virologie, Freiburg, Breisgau, Germany

ABSTRACT- Low doses of ionising radiation may lead to ′non-targeted′ effects observed in non-irradiated cells, as a result of cellular signalling with irradiated cells. Irradiation of non-transformed 208F ′effector′ cells with low doses of ionising radiation stimulates the selective removal of non-irradiated 208Fsrc3 transformed ′target′ cells in co-culture. This intercellular induction of apoptosis (IIA) is observed when effector cells are irradiated with either low LET gamma radiation (0.1 – 2 Gy) or high LET alpha particle radiation (0.0025 – 0.5 Gy) and is irrespective of dose over the ranges studied. The use of scavengers confirms a role for reactive oxygen species (ROS) in the signalling pathways of IIA, consistent with the induction of ROS pathways for IIA by cytokine stimulated effector cells. The selectivity of the apoptotic response is dependent on superoxide derived from a non-phagocytic NADPH oxidase which is constitutively active in the transformed ′target cells′. The addition of a NADPH oxidase inhibitor protects target cells against radiation induced IIA, confirming a role for a non-phagocytic NADPH oxidase. It is suggested that radiation leads to the induction of active TGF- resulting in effector cell ROS signalling and the induction of apoptosis in transformed target cells. These processes may represent a beneficial non-targeted effect of ionising radiation, and a natural anti-tumourogenic defence mechanism to selectively remove pre-cancerous transformed cells.

Key words: Non-targeted effects, Apoptosis, Reactive Oxygen Species, Low Dose

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2005 RRS