We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Modelling the In Vivo and Ex Vivo DNA Damage Response after Internal Irradiation of Blood from Patients with Thyroid Cancer.
- Authors
Schumann, Sarah; Scherthan, Harry; Hartrampf, Philipp E.; Göring, Lukas; Buck, Andreas K.; Port, Matthias; Lassmann, Michael; Eberlein, Uta
- Abstract
This work reports on a model that describes patient-specific absorbed dose-dependent DNA damage response in peripheral blood mononuclear cells of thyroid cancer patients during radioiodine therapy and compares the results with the ex vivo DNA damage response in these patients. Blood samples of 18 patients (nine time points up to 168 h post-administration) were analyzed for radiation-induced γ-H2AX + 53BP1 DNA double-strand break foci (RIF). A linear one-compartment model described the absorbed dose-dependent time course of RIF (Parameters: c characterizes DSB damage induction; k1 and k2 are rate constants describing fast and slow repair). The rate constants were compared to ex vivo repair rates. A total of 14 patient datasets could be analyzed; c ranged from 0.012 to 0.109 mGy−1, k2 from 0 to 0.04 h−1. On average, 96% of the damage is repaired quickly with k1 (range: 0.19–3.03 h−1). Two patient subgroups were distinguished by k1-values (n = 6, k1 > 1.1 h−1; n = 8, k1 < 0.6 h−1). A weak correlation with patient age was observed. While induction of RIF was similar among ex vivo and in vivo, the respective repair rates failed to correlate. The lack of correlation between in vivo and ex vivo repair rates and the applicability of the model to other therapies will be addressed in further studies.
- Subjects
DNA repair; THYROID cancer; MONONUCLEAR leukocytes; CANCER patients; DOUBLE-strand DNA breaks; IRRADIATION; THYROGLOBULIN
- Publication
International Journal of Molecular Sciences, 2024, Vol 25, Issue 10, p5493
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms25105493