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In this article out using Geant4 toolkit. We compared γ-H2AX foci persistence after irradiations with protons to that of γ-rays and carbon ions. ResultsWith the rise of LET values along the therapeutic proton SOBP, the increase of γ-H2AX foci number is detected in the three cell lines up to the distal end of the SOBP, while there is a decrease on its distal fall-off part. With the prolonged incubation time, the number of foci gradually drops tending to attain the residual level. For the maximum number of DNA DSB, irradiation with protons attain higher level than that of γ-rays. Carbon ions produce more DNA DSB than protons but not substantially. The number of residual foci produced by γ-rays is significantly lower than that of protons and particularly carbon ions. Carbon ions do not produce considerably higher number of foci than protons, as it could be expected due to their physical properties. ConclusionsIn situ visualization of γ-H2AX foci reveal creation of more lesions in the three cell lines by clinically relevant proton SOBP than γ-rays. The lack of significant differences in the number of γ-H2AX foci between the proton and carbon ion-irradiated samples suggests an increased complexity of DNA lesions and slower repair kinetics after carbon ions compared to protons. For all three irradiation types, there is no major difference between the three cell lines shortly after irradiations, while later on, the formation of residual foci starts to express the inherent nature of tested cells, therefore increasing discrepancy between them.

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Aim: Newly synthesized platinum(IV) complexes with ethylenediamine-N,N'-diacetate ligands (EDDA-type) (butyl-Pt and pentyl-Pt) were investigated against two cancer (A549 lung, and HTB 140 melanoma) and one noncancerous (MRC-5 embryonic lung fibroblast) human cell lines. Materials and Methods: The effects of these agents were compared with those of cisplatin after 6-, 24-and 48-h treatment. Sulforhodamine-B (SRB) assay was performed to estimate the cytotoxic effect, while the inhibitory effect on cell proliferation was measured using 5-bromo-2,deoxyuridine (BrdU) incorporation assay. Cell cycle analysis was performed by flow cytometry. Type of cell death induced by these agents was determined by electrophoretic analysis of DNA, flow cytometry and by western blot analysis of proteins involved in induction of apoptosis. The effects of gamma irradiation, alone and in combination with platinumbased compounds, were examined by clonogenic and SRB assays. Results: All examined platinum-based compounds had inhibitory and antiproliferative effects on A549 cells, but not on HTB140 and MRC-5 cells. Butyl-Pt, pentyl-Pt and cisplatin arrested the cell cycle in the S-phase and induced apoptotic cell death via regulation of expression of B-cell lymphoma 2 (BCL2) and BCL2-associated X (BAX) proteins. Platinum-based compounds increased the sensitivity of A549 cells to gamma irradiation. Butyl-Pt and pentyl-Pt showed better antitumour effects against A549 cells than did cisplatin, by interfering in cell proliferation and the cell cycle, and by triggering apoptosis. Conclusion: The effects of gamma irradiation on tumour cells may be amplified by pre-treatment of cells with platinum-based compounds.Cisplatin or cis-diamminedichloroplatinum(II) is an effective chemotherapeutic agent that is used in nearly 50% of all patients with cancer (1). It has been used in the fight against ovarian, head and neck, bladder, cervical, oesophageal, as well as against small-cell and non-small-cell lung cancer. The clinical utility of cisplatin is based on the inhibition of the processes that are important for growth and proliferation of cancer cells by binding to DNA molecules and preventing replication, transcription and cell-cycle progression, leading to tumour cell death (2, 3). However, cisplatin administration is associated with adverse effects and therapy resistance. The development of platinum analogues that have similar effectiveness as cisplatin but better toxicity profiles and lack cross-resistance is the major concern in research centres worldwide. Different modifications of cisplatin have been investigated to achieve this aim.Platinum complexes are widely used in cancer therapy research. Approximately 30 platinum(II) and platinum(IV) 5001

Differences in biological response of breast and lung cancer cells to 62 MeV/u therapeutic protons and carbon ions are investigated on MCF-7 and HTB177 cells. Hydroxyl radical scavenger, dimethyl sulfoxide (DMSO) is applied to reduce indirect effects of irradiation, while serum deprivation provided uniformity of cell population. Survival, immunocytochemical, and cell-cycle analysis, changes in protein expression involved in repair and apoptosis are followed. Radiobiological parameters, Bax/Bcl-2 ratio, and increased subG1 fraction show that carbon ions are more efficient in cellular killing than protons. No significant difference in the number of γH2AX foci are found between protons and carbon ions. According to SF2 values, MCF-7 cells are more radioresistant to both ion species compared to HTB177 cells. Cell-cycle analysis and expression of relevant protein markers further confirm somewhat higher radiosensitivity of HTB177 cells compared to MCF-7. DMSO leads to the rise of cell survival and decreases the number of γH2AX foci. Even though there are no significant changes in the number of γH2AX foci after used irradiation types, lesions induced by carbon ions are probably more complex than those produced by protons. DMSO minimizes indirect DNA damage to achieve experimental conditions needed for comparisons of obtained results with numerical simulations.