Assessing radiosensitivity through sublethal damage recovery: a comparison of survival-based and molecular repair kinetics
Bibliographic record
Abstract
Abstract Objective . This study aimed to determine whether the kinetics of sublethal damage recovery after x-ray irradiation, quantified as the repair half time ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mrow> <mml:mrow> <mml:msubsup> <mml:mi mathvariant="normal">T</mml:mi> <mml:mrow> <mml:mi>repair</mml:mi> </mml:mrow> <mml:mrow> <mml:mi>SLD</mml:mi> </mml:mrow> </mml:msubsup> </mml:mrow> </mml:mrow> </mml:math> ) derived from split-dose clonogenic survival, correlates with intrinsic radiosensitivity across four human cancer cell lines: HeLa (cervical), PC3 (prostate), and HCT116 and HT29 (colorectal). In addition, the study compared this survival-based indicator with molecular repair kinetics assessed through γ H2AX and 53BP1 foci clearance. Approach . By using a phenomenological approach, we assessed sublethal damage recovery kinetics, aiming to determine whether this recovery rate could serve as a biomarker for cancer-specific intrinsic radiosensitivity. Cells were subjected to split-dose 4 Gy irradiation delivered in two fractions of 2 Gy across a 0 to 10 h inter-fraction interval range using a Multi-Rad x-ray irradiator with a peak tube voltage of 225 kV. The clonogenic assay was performed following split-dose irradiation of the experimental groups to assess cell survival. Colonies were fixed, stained, and counted ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mrow> <mml:mtext>⩾</mml:mtext> </mml:mrow> </mml:math> 50 cells/colony viable threshold) to calculate survival fractions (SFs) from the four independent experimental runs completed for each cell line. Unirradiated control cells were used to calculate plating efficiency. The measured SF as a function of inter-fraction time was fitted with the Lea–Catcheside modified linear-quadratic model with a half-life of sublethal damage repair, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mrow> <mml:mrow> <mml:msubsup> <mml:mi mathvariant="normal">T</mml:mi> <mml:mrow> <mml:mi>repair</mml:mi> </mml:mrow> <mml:mrow> <mml:mi>SLD</mml:mi> </mml:mrow> </mml:msubsup> </mml:mrow> </mml:mrow> </mml:math> , as a free parameter. To compare this approach to molecular DNA repair kinetics, immunofluorescence-based ionizing radiation-induced foci (IRIF) clearance experiments were performed following single 2 Gy irradiation using the same x-ray source. γ H2AX and 53BP1 foci were quantified from 0.5 to 24 h post-irradiation, and foci clearance half-lives ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mrow> <mml:mrow> <mml:msubsup> <mml:mi mathvariant="normal">T</mml:mi> <mml:mrow> <mml:mi>repair</mml:mi> </mml:mrow> <mml:mrow> <mml:mi>γ</mml:mi> <mml:mi mathvariant="normal">H</mml:mi> <mml:mn>2</mml:mn> <mml:mi>AX</mml:mi> </mml:mrow> </mml:msubsup> </mml:mrow> </mml:mrow> </mml:math> and <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mrow> <mml:mrow> <mml:msubsup> <mml:mi mathvariant="normal">T</mml:mi> <mml:mrow> <mml:mi>repair</mml:mi> </mml:mrow> <mml:mrow> <mml:mn>53</mml:mn> <mml:mi>BP</mml:mi> <mml:mn>1</mml:mn> </mml:mrow> </mml:msubsup> </mml:mrow> </mml:mrow> </mml:math> ) were determined by single-phase exponential decay fitting. Main results . For all measured cell lines, an increase in SF was observed with increasing inter-fraction time. The estimated <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mrow> <mml:mrow> <mml:msubsup> <mml:mi mathvariant="normal">T</mml:mi> <mml:mrow> <mml:mi>repair</mml:mi> </mml:mrow> <mml:mrow> <mml:mi>SLD</mml:mi> </mml:mrow> </mml:msubsup> </mml:mrow> </mml:mrow> </mml:math> varied across cell lines, from <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mrow> <mml:mn>1.07</mml:mn> <mml:mo>±</mml:mo> <mml:mn>0.35</mml:mn> </mml:mrow> </mml:math> h in HT29, to <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mrow> <mml:mn>1.98</mml:mn> <mml:mo>±</mml:mo> <mml:mn>0.94</mml:mn> </mml:mrow> </mml:math> h in HeLa, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mrow> <mml:mn>2.00</mml:mn> <mml:mo>±</mml:mo> <mml:mn>0.30</mml:mn> </mml:mrow> </mml:math> h in PC3, and <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mrow> <mml:mn>3.58</mml:mn> <mml:mo>±</mml:mo> <mml:mn>1.45</mml:mn> </mml:mrow> </mml:math> h in HCT116, indicating different capacities for sublethal damage repair. A negative correlation was measured between <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mrow> <mml:mrow> <mml:msubsup> <mml:mi mathvariant="normal">T</mml:mi> <mml:mrow> <mml:mi>repair</mml:mi> </mml:mrow> <mml:mrow> <mml:mi>SLD</mml:mi> </mml:mrow> </mml:msubsup> </mml:mrow> </mml:mrow> </mml:math> and clonogenic survival at 2 Gy ( <mml:math xmlns:mml="http://www.w3.org/1998/Ma
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".