Comparison of the Medical Uses and Cellular Effects of High and Low Linear Energy Transfer Radiation
Abstract
:1. Introduction
Characteristics of Ionizing Radiation
2. Medical Applications for High- and Low-LET Radiation
2.1. Medical Imaging and the Development of Low-LET Radiation Technology
2.1.1. Relationship between Radiation Energy and Medical Images
2.1.2. Radiation Requirements for Real-Time Imaging of Organ Function with Fluoroscopy and Positron Emission Tomography
2.1.3. Future Imaging Technique Development
2.2. Radiotherapy for Cancer Treatment
Development of Low-LET Photon Radiation for Cancer Treatment
2.3. High-LET Radiation for Cancer Treatment
2.3.1. Development of Brachytherapy Using Radioactive Isotopes
2.3.2. Hadron Therapy: High-LET Radiation Beams for Cancer Treatment
2.4. Techniques for Sparing Normal Tissues during X-ray Cancer Radiotherapy
3. Cellular Effects of High- and Low-LET Radiation
3.1. Cancer Cell Responses to High- and Low-LET Radiation
3.2. Normal, Non-Cancer Cell Responses to High- and Low-LET Radiation
4. Signal Transduction by High and Low LET
4.1. Pathways for DNA Repair
4.2. Regulation of the Cell Cycle: The Gateway for Cell Death or Accelerated Senescence
4.3. Regulation of the Protein Degradation, Endoplasmic Reticulum Stress, and the Unfolded Protein Response Pathway
5. Protein Expression and Gene Transcription by High- and Low-LET Radiation
5.1. Alterations in Protein Levels with Low- and HIGH-LET Radiation
5.2. Regulation of p53 and NF-κB Transcription Factors
5.3. Comparison of Low- and High-LET Radiation Using Genomic Analysis in Cancer Cells
5.4. Comparison of Low- and High-LET Radiation Using Genomic Analysis in Normal Cells
6. Summary and Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Radiation | RBE | Energy Range | References |
---|---|---|---|
Alpha particles | 4–20 | 3.2–9 MeV | [19,74,75] |
Beta particles | 1–3.5 | 0.019–1.7 MeV | [20] |
Slow neutrons | ~2.5–20 | ~10–100 KeV | [18,76,77,78] |
Fast neutrons | ~5–20 | 0.1–3 MeV | [18,76,77,78] |
Protons | ~0.89–3.1 * | 50–1000 MeV | [22,23,79,80] |
Gamma rays | ~1 | 1.2–6 MeV | [19,20] |
X-rays | ~1–1.1 | 200–50 MeV | [19,20,21] |
Isotope | Radiation Type | Half-Life |
---|---|---|
103Pd | 21 KeV gamma * | 17 days |
125I | 27–35 KeV gamma * | 60.25 days |
131Cs | 29.5–33.5 KeV gamma * | 9.7 days |
192Ir | 206–485 KeV gamma * | 74.17 days |
198Au | 314 KeV beta, 412 KeV gamma * | 2.7 days |
226Ra | 47–2450 KeV gamma | 1600 years |
“R” | Definition |
---|---|
Repair | Sublethal DNA damage repair |
Redistribution/reassortment | Redistribution of tumor cells into phases of the cell cycle |
Repopulation | Tumor cell proliferation, symmetrical or asymmetrical division |
Reoxygenation | Normalization of the hypoxic tumor microenvironment |
Radiosensitivity | Susceptibility to radiation-induced cell death due to chromosome number alterations or mutations |
Repair Pathway | Initiating Proteins | DNA Repair | References |
---|---|---|---|
HRR | MRN/CtIP | RPA/BRCA2/RAD51 | [133,144,146,147] |
NHEJ | Ku70/80 | DNA PKcs/XRCC4/Artemis/Pol µ or Pol γ | [133,144,147] |
Alt-EJ | MRN/CtIP | DNA ligase III/PARP1/pol θ | [133,147,148] |
Cell Type | Radiation | Time | Genes | References |
---|---|---|---|---|
Oral squamous cell carcinoma (High v Low LET) * | X-ray (2, 4, 6 Gy) LET ~ 1 KeV/µm 12C (290 MeV/n) (1, 4, 7 Gy) LET = 75 KeV/µm 22Ne (400 MeV/n) (1, 4, 7 Gy) LET = 75 KeV/µm | 4 h | ↑TGFBR2, ↑SMURF2, ↓BMP7, ↑CCND1, ↑F2F3, ↑SPHK1 | [222,236] |
Lymphoma | X-ray (6 MeV, 5 Gy) LET ~ 1 KeV/µm | 24 h | ↑CCL5, ↑ CCL17, ↑CCL22, ↑GNG8, ↑HMOX1, ↑IL32 | [139] |
Lymphoma | Proton (129.3–148.2 MeV/n (5 Gy) LET = 3.5 KeV/µm | 24 h | ↑CCL5, ↑CCL17, ↑CCL22, ↑GNG8, ↑HMOX1, ↑IL32, ↑LRK2, ↑TNF | [139] |
Cell Type | Radiation | Time | Genes | Reference |
---|---|---|---|---|
Peripheral blood mononuclear cells 1 | Gamma (250 keV, 1 Gy) LET ~ 1 KeV/µm | 8 h | ↑PCNA, ↑GADD45A, ↑ASTN2, ↑FDXR, ↑RPS27L, ↑VWCE, ↑PTPN14, ↑EDA2R, ↑CDKN1A, ↑IKBIP, ↑ANKRA2 | [154] |
12C (114.6–158.4 MeV/n, 0.25, 1 Gy) (1, 4, 7 Gy) LET = 60–80 KeV/µm 56Fe (1 GeV/n, 0.25, 1 Gy) LET = 155 KeV/µm | 8 h | ↑PCNA, ↑GADD45A, ↑ASTN2, ↑FDXR, ↑RPS27L, ↑VWCE, ↑PTPN14, ↑EDA2R, ↑CD80, ↑BCL2L1 | [154] | |
Human bronchial epithelial cells 1 | Gamma (662 KeV 1,3 Gy) LET = 0.2 KeV/µm | 1, 4, 12, 24 h | ↑CDKN1A, ↑CCNA1, ↑ BTG2, ↑TRIM22, ↑ INPP5D, ↑GLUL, ↑THBS1, ↓SH3GL3 | [230] |
56Fe (1 GeV/n, 0.5, 1 Gy) LET = 150 KeV/µm 28SI (1 GeV/n, 0.5, 1 Gy) LET = 44 KeV/µm | 1, 4, 12, 24 h | ↑CDKN1A, ↑CCNA1, ↑ BTG2, ↑TRIM22, ↑INPP5D, ↑GLUL, ↓APH1B, ↑BLNK, ↑PLD1, ↑PLD3 | [230] | |
HEK 2 | X-rays (4, 8 Gy, 200 keV) LET ~ 1 KeV/µm | 6 h | ↑TNF, ↑CXCL1, ↑CXCL2, ↑CXCL8, ↑CXCL10, ↑CCL2, ↑CD83, ↑NFKB2, ↑VCAM1, ↑NFKBIA, ↑BIRK3, ↓MAP2K6 | [226] |
22Ne ions (4 Gy, 80 MeV/n) LET = 92 KeV/µm | 6 h | ↑TNF, ↑CXCL1, ↑CXCL8, ↑CXCL10, ↑CCL2, ↑CD83, ↑NFKB2, ↑NFKBIA, ↑VCAM1 | [226] |
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Russ, E.; Davis, C.M.; Slaven, J.E.; Bradfield, D.T.; Selwyn, R.G.; Day, R.M. Comparison of the Medical Uses and Cellular Effects of High and Low Linear Energy Transfer Radiation. Toxics 2022, 10, 628. https://doi.org/10.3390/toxics10100628
Russ E, Davis CM, Slaven JE, Bradfield DT, Selwyn RG, Day RM. Comparison of the Medical Uses and Cellular Effects of High and Low Linear Energy Transfer Radiation. Toxics. 2022; 10(10):628. https://doi.org/10.3390/toxics10100628
Chicago/Turabian StyleRuss, Eric, Catherine M. Davis, John E. Slaven, Dmitry T. Bradfield, Reed G. Selwyn, and Regina M. Day. 2022. "Comparison of the Medical Uses and Cellular Effects of High and Low Linear Energy Transfer Radiation" Toxics 10, no. 10: 628. https://doi.org/10.3390/toxics10100628