Nuclear science has contributed significantly to the development of tumor therapy with heavy charged particles. Interest evolved for neutron therapies in the forties because of the increased radiobiological effectiveness (RBE) compared to photon irradiation. The development of more powerful proton and heavy ion accelerators with higher energies or higher intensities, made new particles for radiation therapy available. Pions, protons, light ions, from helium up to silicon were studied in view of precision dose delivery and increased RBE. Without the parallel development of new diagnostic techniques such as computer tomography (CT) and positron emission tomography (PET) the rapid development would not have been possible. Heavy-charged particle therapy has now come into a consolidation phase. Hospital-based facilities are built by industry, and research institutes focus on refinements in dose delivery and treatment planning, as well as systems for monitoring dose delivery and for dose distribution verification.

Tumor therapy with heavy charged particles

Radioprotective effect of sesamol on γ-radiation induced DNA damage, lipid peroxidation and antioxidants levels in cultured human lymphocytes

In order to characterize the genome-wide transcriptional response of the hyperthermophilic, aerobic crenarchaeote Sulfolobus solfataricus to UV damage, we used high-density DNA microarrays which covered 3,368 genetic features encoded on the host genome, as well as the genes of several extrachromosomal genetic elements. While no significant up-regulation of genes potentially involved in direct DNA damage reversal was observed, a specific transcriptional UV response involving 55 genes could be dissected. Although flow cytometry showed only modest perturbation of the cell cycle, strong modulation of the transcript levels of the Cdc6 replication initiator genes was observed. Up-regulation of an operon encoding Mre11 and Rad50 homologs pointed to induction of recombinational repair. Consistent with this, DNA double-strand breaks were observed between 2 and 8 h after UV treatment, possibly resulting from replication fork collapse at damaged DNA sites. The strong transcriptional induction of genes which potentially encode functions for pilus formation suggested that conjugational activity might lead to enhanced exchange of genetic material. In support of this, a statistical microscopic analysis demonstrated that large cell aggregates formed upon UV exposure. Together, this provided supporting evidence to a link between recombinational repair and conjugation events.

Response of the Hyperthermophilic Archaeon Sulfolobus solfataricus to UV Damage

Background. In vitro RBE values for various high LET radiation types have been determined for many different cell types. Occasionally it is criticized that RBE for a given endpoint cannot be single-value dependent on LET alone, but also on particle species, due to the different dose deposition profiles on microscopic scale. Hence LET is not sufficient as a predictor of RBE, and this is one of the motivations for development of radiobiological models which explicitly depend on the detailed particle energy spectrum of the applied radiation field. The aim of the present study is to summarize the available data in the literature regarding the dependency of RBE on LET for different particles. Method. As RBE is highly dependent on cell type and endpoint, we discriminated the RBE-LET relationship for the three investigated cell lines and at the same endpoint (10% survival in colony formation). Data points were collected from 20, four and four publications for V79, CHO and T1, respectively, in total cover...

In vitro RBE-LET dependence for multiple particle types

Effect of gamma irradiation on optical absorption of nuclear track detectors such as CR-39 was studied in different absorbed doses using ultraviolet–visible (UV–VIS) spectroscopy. The existence of the peaks, their shifting and broadening as a result of gamma irradiation have been discussed. The width of the tail of the localized states in the band gap (Eu) was evaluated using the Urbach edge method. Finally the indirect and direct band gaps in pristine and gamma irradiated CR-39 have been determined. The values of the indirect band gap have been found to be lower than the corresponding values of the direct band gap. A decrease in the optical energy gap with increasing gamma absorbed dose can be discussed on the basis of gamma-irradiation-induced defects in CR-39. The correlation between the optical band gap and the number of carbon atoms in a cluster with the modified Tauc's equation has been discussed in the case of CR-39.

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Gamma-induced modification on optical band gap of CR-39 SSNTD

The formation of carbonaceous clusters in ion-irradiated polymer films was investigated extensively. Information about these clusters may be obtained with ultraviolet–visible (UV–vis) spectroscopy. The optical band gap (Eg), calculated from the absorption edge of the UV spectra of these polymers, can be correlated to the number of carbon atoms (N) in a cluster with the modified Tauc equation. The structure of the cluster is also related to Eg; for example, a six-membered-benzene-ring-type structure has an Eg of ≈5.3 eV, whereas a buckminsterfullerene-type structure has an Eg of ≈4.9 eV. These clusters are responsible for the electrical conductivity in these films. In this work, polycarbonate films (20 μm thick) were irradiated with 45-MeV Li ions at fluences of 1 × 1012 to 1 × 1013 cm−2 and were characterized with UV–vis spectroscopy and impedance measurements. The Eg values, calculated from the absorption edge in the 280–315-nm region with the Tauc relation, varied from 4.39 to 4.35 eV for the pristine and various irradiated samples, respectively. The cluster size showed a range of 60–62 carbon atoms per cluster. The sheet conductivity (σdc) and loss (tan δ) values of 10−16 Ω−1cm−1 and 10−3 for the pristine sample changed to 10−15 Ω−1cm−1 and 10−2, respectively, for the irradiated samples. This increase in the values of σdc and tan δ may be correlated to the increase in the size of the carbonaceous clusters. This study provides insight into the mechanism of electrical conductivity in irradiated polymers. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 38: 1589–1594, 2000

Study of carbonaceous clusters in irradiated polycarbonate with UV–vis spectroscopy

Chinese hamster V79 cells were exposed to high LET (linear energy transfer) 16 O-beam (625 keV/μm) radiation in the dose range of 0–9.83 Gy. Cell survival, micronuclei (MN), chromosomal aberrations (CA) and induction of apoptosis were studied as a follow up of our earlier study on high LET radiations ( 7 Li-beam of 60 keV/μm and 12 C-beam of 295 keV/μm) as well as 60 Co γ-rays. Dose dependent decline in surviving fraction was noticed along with the increase of MN frequency, CA frequency as well as percentage of apoptosis as detected by nuclear fragmentation assay. The relative intensity of DNA ladder, which is a useful marker for the determination of the extent of apoptosis induction, was also increased in a dose dependent manner. Additionally, expression of tyrosine kinase lck-1 gene, which plays an important role in response to ionizing radiation induced apoptosis, was increased with the increase of radiation doses and also with incubation time. The present study showed that all the high LET radiations were generally more effective in cell killing and inflicting other cytogenetic damages than that of low LET γ-rays. The dose response curves revealed that 7 Li-beam was most effective in cell killing as well as inducing other nuclear damages followed by 12 C, 16 O and 60 Co γ-rays, in that order. The result of this study may have some application in biological dosimetry for assessment of genotoxicity in heavy ion exposed subjects and in determining suitable doses for radiotherapy in cancer patients where various species of heavy ions are now being generally used.

Cell killing, nuclear damage and apoptosis in Chinese hamster V79 cells after irradiation with heavy-ion beams of 16O, 12C and 7Li

Cellular membranes are vital elements, and their integrity is extremely essential for the viability of the cells. We studied the effects of high linear energy transfer (LET) radiation on the membranes. Rabbit erythrocytes (1×107 cells/ml) and microsomes (0.6 mg protein/ml) prepared from liver of rats were irradiated with 7Li ions of energy 6.42 MeV/u and 16O ions of energy 4.25 MeV/u having maximum LET values of 354 keV/μm and 1130 keV/μm, respectively. 7Li- and 16O-induced microsomal lipid peroxidation was found to increase with fluence. The 16O ions were more effective than 7Li ions, which could be due to the denser energy distribution in the track and the yield of free radicals. These findings suggested that the biological membranes could be peroxidized on exposure to high-LET radiation. Inhibition of the lipid peroxidation was observed in the presence of a membrane-active drug, chlorpromazine (CPZ), which could be due to scavenging of free radicals (mainly HO⋅ and ROO⋅), electron donation, and hydrogen transfer reactions. The 7Li and 16O ions also induced hemolysis in erythrocytes. The extent of hemolysis was found to be a function of time and fluence, and showed a characteristic sigmoidal pattern. The 16O ions were more effective in the lower fluence range than 7Li ions. These results were compared with lipid peroxidation and hemolysis induced by gamma-radiation.

Effect of high linear energy transfer radiation on biological membranes.

Purpose: To study the effects of 12C-beam of 295 keV/µm (57.24 MeV) on M5 and Chinese hamster V79 cells by using cytogenetic assays like micronuclei (MN) induction, chromosomal aberrations (CA) and apoptosis. Additionally, the relative survival of these two cell lines was tested by the colony forming ability of the cells, with a view to understanding the mechanism of cellular damages that lead to difference in cell survival.Materials and methods: Confluent cells were irradiated with 12C-beam at various doses using 15UD Pelletron accelerator. Cell survival was studied by the colony forming ability of cells. MN assay was done by fluorescent staining. Different types of chromosomal aberrations in metaphase cells were scored at 12 h after irradiation. Apoptosis was measured at different post irradiation times as detected by nuclear fragmentation and DNA ladder was prepared after 48 h of incubation.Results: Dose-dependent decrease in surviving fractions was found in both the cell lines. However, the surviving ...

Response to high LET radiation 12C (LET, 295 keV/microm) in M5 cells, a radio resistant cell strain derived from Chinese hamster V79 cells.

Oxygen beams are high linear energy transfer (LET) radiation characterized by higher relative biological effectiveness than low LET radiation. The aim of the current study was to determine the signaling differences between γ- and oxygen ion-irradiation. Activation of various signaling molecules was looked in A549 lung adenocarcinoma cells irradiated with 2Gy oxygen, 2Gy or 6Gy γ-radiation. Oxygen beam was found to be three times more cytotoxic than γ-radiation. By 4h there was efficient repair of DNA in A549 cells exposed to 2Gy or 6Gy gamma radiation but not in cells exposed to 2Gy oxygen beam as determined by γ-H2AX counting. Number of ATM foci was found to be significantly higher in cells exposed to 2Gy oxygen beam. Percentage of cells showing ATR foci were more with gamma however number of foci per cell were more in case of oxygen beam. Oxygen beam irradiated cells showed phosphorylation of Chk1, Chk2 and p53. Many apoptotic nuclei were seen by DAPI staining in cells exposed to oxygen beam. The noteworthy finding of this study is the activation of the sensor proteins, ATM and ATR by oxygen irradiation and the significant activation of Chk1, Chk2 and p53 only in the oxygen beam irradiated cells.

A. Sarma

Papers

Study of carbonaceous clusters in irradiated polycarbonate with UV–vis spectroscopy

Cell killing, nuclear damage and apoptosis in Chinese hamster V79 cells after irradiation with heavy-ion beams of 16O, 12C and 7Li

Effect of high linear energy transfer radiation on biological membranes.

Response to high LET radiation 12C (LET, 295 keV/microm) in M5 cells, a radio resistant cell strain derived from Chinese hamster V79 cells.

Activation of DNA damage response signaling in lung adenocarcinoma A549 cells following oxygen beam irradiation.