Induction of reproductive cell death and chromosome aberrations in radioresistant tumour cells by carbon ions

Hofman-Hüther, Hana; Scholz, M.; Rave-Fränk, Margret; Virsik-Köpp, Patricia

doi:10.1080/09553000410001702319

Cited by 12 publications

(6 citation statements)

References 39 publications

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“…However, repair kinetics (investigated at later time points) have shown a delayed or less successful repair of DSBs after high-LET radiation ( 16 , 17 ). Therefore, particle irradiation can be effective in inducing cell death even in highly radioresistant cells ( 18 ). One of the factors that plays a major role in determining radiosensitivity is p53.…”

Section: Introductionmentioning

confidence: 99%

Higher Initial DNA Damage and Persistent Cell Cycle Arrest after Carbon Ion Irradiation Compared to X-irradiation in Prostate and Colon Cancer Cells

et al. 2016

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The use of charged-particle beams, such as carbon ions, is becoming a more and more attractive treatment option for cancer therapy. Given the precise absorbed dose-localization and an increased biological effectiveness, this form of therapy is much more advantageous compared to conventional radiotherapy, and is currently being used for treatment of specific cancer types. The high ballistic accuracy of particle beams deposits the maximal dose to the tumor, while damage to the surrounding healthy tissue is limited. In order to better understand the underlying mechanisms responsible for the increased biological effectiveness, we investigated the DNA damage and repair kinetics and cell cycle progression in two p53 mutant cell lines, more specifically a prostate (PC3) and colon (Caco-2) cancer cell line, after exposure to different radiation qualities. Cells were irradiated with various absorbed doses (0, 0.5, and 2 Gy) of accelerated 13C-ions at the Grand Accélérateur National d’Ions Lourds facility (Caen, France) or with X-rays (0, 0.1, 0.5, 1, 2, and 5 Gy). Microscopic analysis of DNA double-strand breaks showed dose-dependent increases in γ-H2AX foci numbers and foci occupancy after exposure to both types of irradiation, in both cell lines. However, 24 h after exposure, residual damage was more pronounced after lower doses of carbon ion irradiation compared to X-irradiation. Flow cytometric analysis showed that carbon ion irradiation induced a permanent G2/M arrest in PC3 cells at lower doses (2 Gy) compared to X-rays (5 Gy), while in Caco-2 cells the G2/M arrest was transient after irradiation with X-rays (2 and 5 Gy) but persistent after exposure to carbon ions (2 Gy).

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Section: Introductionmentioning

confidence: 99%

Higher Initial DNA Damage and Persistent Cell Cycle Arrest after Carbon Ion Irradiation Compared to X-irradiation in Prostate and Colon Cancer Cells

et al. 2016

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“…Several studies [21, 34, 35, 46] have reported linear relationships between foci numbers or relative γ-H2AX fluorescence and dose using X-rays but generally at high doses. Using a series of cancer cell lines, it was concluded that the presence of γ-H2AX foci at long times after γ-irradiation of exponentially growing monolayers may not always signify the presence of a DSB [38].…”

Section: Introductionmentioning

confidence: 99%

“…These results are well in line with findings of Hofman-Huther et al . (2004) who observed that the frequencies of cells containing complex chromosomal aberrations increased dramatically after irradiation of radio-resistant tumor cells with carbon ions versus X-rays [46]. One decade earlier, it was demonstrated that dense ionizing radiation, such as heavy ions, is much more efficient than sparsely ionizing radiation in the induction of complex-type exchanges [47].…”

Section: Introductionmentioning

confidence: 99%

Differences in Phosphorylated Histone H2AX Foci Formation and Removal of Cells Exposed to Low and High Linear Energy Transfer Radiation

Schmid

Zlobinskaya²,

Multhoff³

2012

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The use of particle ion beams in cancer radiotherapy has a long history. Today, beams of protons or heavy ions, predominantly carbon ions, can be accelerated to precisely calculated energies which can be accurately targeted to tumors. This particle therapy works by damaging the DNA of tissue cells, ultimately causing their death. Among the different types of DNA lesions, the formation of DNA double strand breaks is considered to be the most relevant of deleterious damages of ionizing radiation in cells. It is well-known that the extremely large localized energy deposition can lead to complex types of DNA double strand breaks. These effects can lead to cell death, mutations, genomic instability, or carcinogenesis. Complex double strand breaks can increase the probability of mis-rejoining by NHEJ. As a consequence differences in the repair kinetics following high and low LET irradiation qualities are attributed mainly to quantitative differences in their contributions of the fast and slow repair component. In general, there is a higher contribution of the slow component of DNA double strand repair after exposure to high LET radiation, which is thought to reflect the increased amount of complex DNA double strand breaks. These can be accurately measured by the γ-H2AX assay, because the number of phosphorylated H2AX foci correlates well with the number of double strand breaks induced by low or / and high LET radiation.

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“…Indeed, higher amounts of basal DNA damage, as evidenced by an increase in the number of basal γ -H2AX foci is often observed in different types of tumors ( Warters et al, 2005 ; Bonner et al, 2008 ). A dramatic increase in the frequency of complex CAs in radio-resistant tumor cells was observed after carbon ion irradiation ( Hofman-Huther et al, 2004 ). Subsequent cytogenetic studies revealed exposure to HZE radiation can cause a much higher level of complex chromosomal rearrangements ( Loucas and Cornforth, 2001 ; Durante et al, 2002 ).…”

Section: Dna Damage Response Focimentioning

confidence: 99%

Evaluating biomarkers to model cancer risk post cosmic ray exposure

Sridharan

Asaithamby

Blattnig

et al. 2016

Life Sciences in Space Research

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Robust predictive models are essential to manage the risk of radiation-induced carcinogenesis. Chronic exposure to cosmic rays in the context of the complex deep space environment may place astronauts at high cancer risk. To estimate this risk, it is critical to understand how radiation-induced cellular stress impacts cell fate decisions and how this in turn alters the risk of carcinogenesis. Exposure to the heavy ion component of cosmic rays triggers a multitude of cellular changes, depending on the rate of exposure, the type of damage incurred and individual susceptibility. Heterogeneity in dose, dose rate, radiation quality, energy and particle flux contribute to the complexity of risk assessment. To unravel the impact of each of these factors, it is critical to identify sensitive biomarkers that can serve as inputs for robust modeling of individual risk of cancer or other long-term health consequences of exposure. Limitations in sensitivity of biomarkers to dose and dose rate, and the complexity of longitudinal monitoring, are some of the factors that increase uncertainties in the output from risk prediction models. Here, we critically evaluate candidate early and late biomarkers of radiation exposure and discuss their usefulness in predicting cell fate decisions. Some of the biomarkers we have reviewed include complex clustered DNA damage, persistent DNA repair foci, reactive oxygen species, chromosome aberrations and inflammation. Other biomarkers discussed, often assayed for at longer points post exposure, include mutations, chromosome aberrations, reactive oxygen species and telomere length changes. We discuss the relationship of biomarkers to different potential cell fates, including proliferation, apoptosis, senescence, and loss of stemness, which can propagate genomic instability and alter tissue composition and the underlying mRNA signatures that contribute to cell fate decisions. Our goal is to highlight factors that are important in choosing biomarkers and to evaluate the potential for biomarkers to inform models of post exposure cancer risk. Because cellular stress response pathways to space radiation and environmental carcinogens share common nodes, biomarker-driven risk models may be broadly applicable for estimating risks for other carcinogens.

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Induction of reproductive cell death and chromosome aberrations in radioresistant tumour cells by carbon ions

Cited by 12 publications

References 39 publications

Higher Initial DNA Damage and Persistent Cell Cycle Arrest after Carbon Ion Irradiation Compared to X-irradiation in Prostate and Colon Cancer Cells

Higher Initial DNA Damage and Persistent Cell Cycle Arrest after Carbon Ion Irradiation Compared to X-irradiation in Prostate and Colon Cancer Cells

Differences in Phosphorylated Histone H2AX Foci Formation and Removal of Cells Exposed to Low and High Linear Energy Transfer Radiation

Evaluating biomarkers to model cancer risk post cosmic ray exposure

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