Dataset Information

Ne-22 Ion-Beam Radiation Damage to DNA: From Initial Free Radical Formation to Resulting DNA-Base Damage.

ABSTRACT: We report on the physicochemical processes and the products of DNA damage involved in Ne-22 ion-beam radiation of hydrated (12 ± 3 H₂O/nucleotide) salmon testes DNA at 77 K. Free radicals trapped at 77 K were identified using electron spin resonance (ESR) spectroscopy. The measurement of DNA damage using two different techniques of mass spectrometry revealed the formation of numerous DNA products. Results obtained by ESR spectroscopy showed that as the linear energy transfer (LET) of the ion-beam radiation increases along the beam track, the production of DNA radicals correspondingly increases until just before the Bragg peak is reached. Yields of DNA products along the ion-beam track were in excellent agreement with the radical production. This work is the first to use the combination of ESR spectroscopy and mass spectrometric techniques enabling a better understanding of mechanisms of radiation damage to DNA by heavy ion beams detailing the formation of DNA free radicals and their subsequent products.

SUBMITTER: Kant M

PROVIDER: S-EPMC8246699 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Ne-22 Ion-Beam Radiation Damage to DNA: From Initial Free Radical Formation to Resulting DNA-Base Damage.

Kant Melis M Jaruga Pawel P Coskun Erdem E Ward Samuel S Stark Alexander D AD Baumann Thomas T Becker David D Adhikary Amitava A Sevilla Michael D MD Dizdaroglu Miral M

ACS omega 20210614 25

We report on the physicochemical processes and the products of DNA damage involved in Ne-22 ion-beam radiation of hydrated (12 ± 3 H<sub>2</sub>O/nucleotide) salmon testes DNA at 77 K. Free radicals trapped at 77 K were identified using electron spin resonance (ESR) spectroscopy. The measurement of DNA damage using two different techniques of mass spectrometry revealed the formation of numerous DNA products. Results obtained by ESR spectroscopy showed that as the linear energy transfer (LET) of ...[more]

PMID: 34235332

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Project description:BackgroundThis study aimed to compare the results of irradiation with protons versus irradiation with carbon ions in a raster scan technique in patients with skull base chordomas and to identify risk factors that may compromise treatment results.MethodsA total of 147 patients (85 men, 62 women) were irradiated with carbon ions (111 patients) or protons (36 patients) with a median dose of 66 Gy (RBE (Relative biological effectiveness); carbon ions) in 4 weeks or 74 Gy (RBE; protons) in 7 weeks at the Heidelberg Ion Beam Therapy Center (HIT) in Heidelberg, Germany. The median follow-up time was 49.3 months. All patients had gross residual disease at the beginning of RT. Compression of the brainstem was present in 38%, contact without compression in 18%, and no contact but less than 3 mm distance in 16%. Local control and overall survival were evaluated using the Kaplan-Meier Method based on scheduled treatment (protons vs. carbon ions) and compared via the log rank test. Subgroup analyses were performed to identify possible prognostic factors.ResultsDuring the follow-up, 41 patients (27.9%) developed a local recurrence. The median follow-up time was 49.3 months (95% CI: 40.8-53.8; reverse Kaplan-Meier median follow-up time 56.3 months, 95% CI: 51.9-60.7). No significant differences between protons and carbon ions were observed regarding LC, OS, or overall toxicity. The 1‑year, 3‑year, and 5‑year LC rates were 97%, 80%, and 61% (protons) and 96%, 80%, and 65% (carbon ions), respectively. The corresponding OS rates were 100%, 92%, and 92% (protons) and 99%, 91%, and 83% (carbon ions). No significant prognostic factors for LC or OS could be determined regarding the whole cohort; however, a significantly improved LC could be observed if the tumor was > 3 mm distant from the brainstem in patients presenting in a primary situation.ConclusionOutcomes of proton and carbon ion treatment of skull base chordomas seem similar regarding tumor control, survival, and toxicity. Close proximity to the brainstem might be a negative prognostic factor, at least in patients presenting in a primary situation.

Project description:NIMA-related kinases, or NEKs, are a family of Ser/Thr protein kinases involved in cell cycle and mitosis, centrosome disjunction, primary cilia functions, and DNA damage responses among other biological functional contexts in vertebrate cells. In human cells, there are 11 members, termed NEK1 to 11, and the research has mainly focused on exploring the more predominant roles of NEKs in mitosis regulation and cell cycle. A possible important role of NEKs in DNA damage response (DDR) first emerged for NEK1, but recent studies for most NEKs showed participation in DDR. A detailed analysis of the protein interactions, phosphorylation events, and studies of functional aspects of NEKs from the literature led us to propose a more general role of NEKs in DDR. In this review, we express that NEK1 is an activator of ataxia telangiectasia and Rad3-related (ATR), and its activation results in cell cycle arrest, guaranteeing DNA repair while activating specific repair pathways such as homology repair (HR) and DNA double-strand break (DSB) repair. For NEK2, 6, 8, 9, and 11, we found a role downstream of ATR and ataxia telangiectasia mutated (ATM) that results in cell cycle arrest, but details of possible activated repair pathways are still being investigated. NEK4 shows a connection to the regulation of the nonhomologous end-joining (NHEJ) repair of DNA DSBs, through recruitment of DNA-PK to DNA damage foci. NEK5 interacts with topoisomerase IIβ, and its knockdown results in the accumulation of damaged DNA. NEK7 has a regulatory role in the detection of oxidative damage to telomeric DNA. Finally, NEK10 has recently been shown to phosphorylate p53 at Y327, promoting cell cycle arrest after exposure to DNA damaging agents. In summary, this review highlights important discoveries of the ever-growing involvement of NEK kinases in the DDR pathways. A better understanding of these roles may open new diagnostic possibilities or pharmaceutical interventions regarding the chemo-sensitizing inhibition of NEKs in various forms of cancer and other diseases.

Dataset Information

Ne-22 Ion-Beam Radiation Damage to DNA: From Initial Free Radical Formation to Resulting DNA-Base Damage.

Publications

Ne-22 Ion-Beam Radiation Damage to DNA: From Initial Free Radical Formation to Resulting DNA-Base Damage.

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