Exploration of ‘over kill effect’ of high-LET Ar- and Fe-ions by evaluating the fraction of non-hit cell and interphase death
Open accessAbstract
The reason why RBE for cell killing fell to less than unity (1.0) with very high-LET heavy-ions ((40)Ar: 1,640 keV/microm; (56)Fe: 780, 1,200, 2,000 keV/microm) was explored by evaluating the fraction of non-hit cell (time-lapse observation) and cells undergoing interphase death (calculation based on our previous data). CHO cells were exposed to 4 Gy (30% survival dose) of Ar (1,640 keV/microm) or Fe-ions (2,000 keV/microm). About 20% of all cells were judged to be non-hit, and about 10% cells survived radiation damage. About 70% cells died after dividing at least once (reproductive death) or without dividing (interphase death). RBE for reproductive (RBE[R]) and interphase (RBE[I]) death showed a similar LET dependence with maximum around 200 keV/microm. In this LET region, at 30% survival level, about 10% non-survivors underwent interphase death. The corresponding value for very high-LET Fe-ions (2,000 keV/microm) was not particularly high (approximately 15%), whereas that for X-rays was less than 3%. However, reproductive death (67%) predominated over interphase death (33%) even in regard to rather severely damaged cells (1% survival level) after exposure to Fe-ions (2,000 keV/microm). These indicate that interphase death is a type of cell death characteristic for the cells exposed to high-LET radiation and is not caused by "cellular over kill effect". Both NHF37 (non-hit fraction at 37% survival) and inactivation cross-section for reproductive death (sigma[R]) began to increase when LET exceeded 100 keV/microm. The exclusion of non-hit fraction in the calculation of surviving fraction partially prevented the fall of RBE[R] when LET exceeded 200 keV/microm. On the other hand, the mean number of lethal damage per unit dose (NLD/Gy) showed the same LET-dependent pattern as RBE[R]. These suggest that the increase in non-hit fraction and sigma[R] with an increasing LET is caused by enhanced clustering of ionization and DNA damage which lowers the energy efficiency for producing damage and RBE.
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- Authors
- MEHNATI, P., MORIMOTO, S., YATAGAI, F., FURUSAWA, Y., KOBAYASHI, Y., WADA, S., KANAI, T., HANAOKA, F., & SASAKI, H.
- Affiliations
- Kyushu University (JP)
- RIKEN (JP)
- National Institute of Radiological Sciences (JP)
- Corresponding author
- SASAKI, Hiroshi
- Venue
- Journal of Radiation Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2005
- Volume
- 46
- Issue
- 3
- Pages
- 343-350
- ISSN
- 0449-3060 (ISSN-L)
- 1349-9157
- OpenAlex
- W2152649674
- Cited by
- 40
- References
- 21
- Citations by year
- 2025: 3 · 2023: 2 · 2022: 5 · 2021: 2 · 2020: 3 · 2018: 4 · 2017: 2 · 2016: 1 · 2015: 2 · 2014: 1 · 2012: 4
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Radiation Research (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- Funders
- RIKEN
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Radiation Therapy and Dosimetry
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Physical Sciences › Engineering › Computational Mechanics › Ion-surface interactions and analysis
- Keywords
- relative biological effectiveness, high-LET radiation, argon ions, iron ions, inactivation cross section, CHO cells, radiation-induced cell death, X-ray comparison
- MeSH terms
- Animals, Argon, Cell Survival, Cricetulus, Dose-Response Relationship, Radiation, Cricetinae, Interphase, Ions, Iron, Radiation Dosage, Radiation, Ionizing, CHO Cells, Apoptosis, Linear Energy Transfer, Heavy Ions
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