ESTRO 2023 - Abstract Book

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ESTRO 2023

This effect lasted up to 14 days after radiation of ALI-PBEC (figure 2). In contrast, IR did not increase mRNA levels for markers of epithelial-mesenchymal transition (EMT; ZEB-1, SLUG, SNAIL, vimentin) or inflammation (IL-1 β , IL-8, VEGF) in the ALI-PBEC model. There was also no upregulation of secreted proteins IL-6, IL-8 or fibronectin. Furthermore, there were no changes in morphology and barrier function (Trans Epithelial Electrical Resistance; TEER) following IR, indicating that it did not cause cytotoxicity. IR did cause double stranded DNA breaks, increasing with radiation dose as measured by immunofluorescent staining of γ H2Ax-foci.

Conclusion In conclusion, epithelial progenitor cell function as assessed by organoid formation capacity is strongly reduced by IR and persists for at least 14 days. This effect is not accompanied by IR-induced cytotoxicity, release of pro-inflammatory mediators or EMT. This effect on progenitor cell function could be a lead to further delineate RILI.

PO-2205 Histopathological examination of proton radiation-induced late effects in mice legs

C. Bang Overgaard 1 , D. Mortensen 2 , J. Randel Nyengaard 2,3 , T. Tramm 2 , B. Singers Sørensen 1,4

1 Aarhus University Hospital, Experimental Clinical Oncology, Aarhus, Denmark; 2 Aarhus University Hospital, Pathology, Aarhus, Denmark; 3 Aarhus University, Core Center for Molecular Morphology, Section for Stereology and Microscopy, Clinical Medicine, Aarhus, Denmark; 4 Aarhus University Hospital, Danish Centre for Particle Therapy, Aarhus, Denmark Purpose or Objective Radiation-induced fibrosis is a common chronic and progressive side effect post radiotherapy. It is important to understand the radiobiological rationale for chronic effects of proton radiation to improve the quality of life of multiple patients. The challenge is to compare the observable changes with the actual pathological tissue changes post radiation. The purpose of this exploratory study was to test a procedure for histochemical and stereological examination of proton-irradiated mice legs that received different doses and compare this to a leg contraction assay. Materials and Methods The right hindlimb of 4 mice were irradiated with a single high PBS proton dose of 27 Gy, 31 Gy, 33 Gy or 45 Gy. They exhibited different degrees of late effect severity in a previously published leg contraction assay (score 2: low, score 3: medium, score 4: severe). The treated right hindlimb and the control left leg were harvested post one year of functional late effect follow up. Three cross sections of the legs were cut, namely the upper leg (above ancle joint), the ancle joint and the foot. The tissue sections were stained with Hematoxylin-Eosin or Masson’s Trichrome to evaluate their total area, area fraction of connective- and adipose tissue, epidermal thickness, and total skin adnexa (hair follicles and glands) profile count. Area fraction was evaluated using stereological point sampling. Epidermal thickness was measured from the basal layer up to and including the granular layer with orthogonal intercept length. Total tissue section area was estimated by 2-dimensional nucleator.