Abstract Book

S1254

ESTRO 37

Electronic Poster: Radiobiology track: Radiobiology of skin

Conclusion Under radiation injury, local PGE 2 pretreatment might protect hair follicle TACs against radiation injury through modulating their cell cycles and the preserved TACs can serve as 'reserve stem cells” to regenerate the lost structures to resume anagen growth, thus bypassing the long downtime needed to rest hair cycles through telogen for bulge stem cell activation.

EP-2270 Novel protective effect of prostaglandin for timely hair follicle regeneration from radiation injury S. Lai 1,2 , W.Y. Huang 1 , S.Y. Chen 1 , S.J. Lin 1,3,4 1 National Taiwan University, Institute of Biomedical Engineering- College of Medicine and College of Engineering, Taipei, Taiwan 2 National Taiwan University Hospital and College of Medicine, Division of Radiation oncology- Department of Oncology, Taipei, Taiwan 3 National Taiwan University, Research Center for Developmental Biology and Regenerative Medicine, Taipei, Taiwan 4 National Taiwan University Hospital and College of Medicine, Department of Dermatology, Taipei, Taiwan Purpose or Objective Tissue stem cells are often responsible for regeneration after injury. The highly proliferative hair follicles (HFs) are one of the organs that are sensitive to radiation and hair loss is a common side effect that still lacks an effective treatment. Due to the quiescent nature of bulge stem cells in HFs, their activation requires considerable time and signaling relays to reset hair cycles. Treatment that can fasten the regenerative process will help to shorten the downtime before functional recovery. In this work, we try to characterize the novel effect of prostaglandin, which may help for timely regeneration of HFs following radiation injury. Material and Methods Single dose of gamma irradiation (8.5Gy) were given to C57BL/6 mice in the early full anagen(growth phase). A single dose of dmPGE 2 (A stabilized derivative of prostaglandin E2, 16,16-dimethyl-PGE 2 ) is given locally at 2hr before irradiation. Skin samples will be harvested at the indicated time points following irradiation for histological analysis. The gross appearance of hair was serially recorded. The dynamics at different time points was analyzed by histology, immunohistochemical analysis and lineage tracing. Cell behavior was modulated by pharmacological and genetic tools in vivo. Results We observed that local prostaglandin E2 (PGE 2 ) pretreatment could reduce hair loss from radiation injury by preventing entry into catagen (regression phase) and telogen (resting phase) ( Figure1 ). Surprisingly, quiescent hair follicle bulge stem cells were not activated. Instead, the dystrophy of hair bulbs where hair follicle transit amplifying cells (TACs) reside was reduced and concentric layers of anagen hair follicle structures were quickly regenerated. The proliferation of TACs was halted by PGE 2 pretreatment and immunostaining of cell cycle markers suggesting PGE 2 might reduce the radiosensitivity of TACs through cell cycle modulation.

Electronic Poster: Radiobiology track: Normal tissue radiobiology (others)

EP-2271 The role of mitochondria in the non-targeted effect of ionizing radiation S. Miranda 1 , M. Correia 2 , A.G. Dias 3 , P. Boaventura 2 , V. Máximo 2 1 Instituto Português de Oncologia do Porto Francisco Gentil- EPE, Radiotherapy, Porto, Portugal 2 i3S, Cancer Signalling and Metabolism Group, Porto, Portugal 3 IPO-Porto, Serviço de Física Médica, Porto, Portugal Purpose or Objective Radiotherapy is a clinical modality dealing with the use of ionizing radiation (IR) for the treatment of cancer patients. It aims delivering a precise dose to a defined volume with minimal damage to the surrounding healthy tissue. In radiobiology, the classical view of DNA as the target for radiation has been changing with emerging evidence showing radiobiological effects in cells not traversed by ionizing radiation. These effects have been described as bystander effects and the term comprises a variety of changes which occur in cells which were not directly irradiated. Mitochondria are essential organelles for cellular homeostasis, not only for ATP production but also as intermediaries in several signalling pathways. Some authors have raised the veil of the role of mitochondria in bystander signalling by showing that the production of a bystander effect in bystander cells was not observed when the irradiated counterparts did not have mitochondrial DNA (mtDNA). We proposed to investigate the role of mitochondria in the production of a bystander signal using an osteosarcoma cell line (143B) manipulated in order to obtain cybrids with different The cell lines used were: normal mtDNA cybrid (Cy143Bwt); a cell line with mtDNA mutated in the A3243T tRNA Leu(UUR) gene, characteristic of the hereditary syndrome MELAS, and a cell line without mtDNA (143B- ρ0). We irradiated cells with megavoltage X-ray (6Mv) (with 0.2Gy and 2.0Gy) and characterized their response to direct IR through cellular growth, ROS production, mitochondrial membrane potential alterations, DNA double strand breaks and apoptosis. To induce a bystander effect in non-irradiated cells, we used media from irradiated cells to treat bystander non-irradiated cells, analysing DNA double strand breaks and apoptosis. Results Irradiation induced an increased DNA damage in all three cell lines but increased apoptosis was not observed. Conditioned media increased DNA damage but the effect of the damage was different according to the cell line it derived: Cy143bwt irradiated with 0.2Gy conditioned media induced more damage in Cy143Bwt, but in Cy143BMELAS, 2.0Gy conditioned media induced more damage. Cy143Bwt conditioned media induced similar mitochondrial status. Material and Methods