Exposure to toxic chemicals, especially chemotherapeutic drugs, may induce several DNA lesions, including DNA interstrand crosslinks. These crosslinks are considered toxic lesions to the dividing cells since they can ...Exposure to toxic chemicals, especially chemotherapeutic drugs, may induce several DNA lesions, including DNA interstrand crosslinks. These crosslinks are considered toxic lesions to the dividing cells since they can induce mutations, chromosomal rearrangements, and cell death. Many DNA interstrand crosslinks lesions can be generated by platinum-based chemotherapeutic agents. Satraplatin is a novel orally administered platinum-based chemotherapeutic agent. In the present study, we investigated DNA interstrand crosslinks lesions induced by oxaliplatin and satraplatin in lymphocytes obtained from colorectal cancer patients and healthy volunteers. Satraplatin demonstrated an increase in interstrand crosslinks in a dose-dependent manner in the Comet assay (p in vitro. Here, to the best of our knowledge we report for the first time evidence of DNA double strand breaks formation as a possible molecular mechanism of action for satraplatin.展开更多
Aim:Cancer stem cells(CSCs)are highly resistant to chemotherapy andγ-irradiation.Neutrons have a high linear energy transfer,which can lead to extensive damage to the DNA of tumor cells and CSCs.The aim of this work ...Aim:Cancer stem cells(CSCs)are highly resistant to chemotherapy andγ-irradiation.Neutrons have a high linear energy transfer,which can lead to extensive damage to the DNA of tumor cells and CSCs.The aim of this work was to compare the sensitivity of MCF-7 human breast adenocarcinoma cells and CSCs toγ-andγ,n-irradiation.Methods:To increase the number of CSCs,MCF-7 cells were cultured as mammospheres.γ-irradiation was carried out in a GUT-200M device(^(60)Co source)in the dose range of 1-8 Gy at a dose rate of 0.75 Gy/min.γ,n-irradiation was carried out in an IR-8 reactor in the dose range of 0.05-2 Gy at a dose rate of 0.06 Gy/min.DNA DSB formation was assessed by the level ofγH2AX foci using fluorescence microscopy and flow cytometry.CSCs were identified by flow cytometry as CD44^(+)/CD24^(-/low) cells.Results:We showed thatγ,n-irradiation induced the formation ofγH2AX foci of a larger size than didγ-irradiation and led to more severe DNA damage per 1 Gy.Moreover,γ,n-radiation was found to have a high relative biological effectiveness(RBE)as assessed by the cell survival rate,the number of CSCs in culture,and the ability of CSCs to repopulate.The highest RBE of neutron radiation was observed at low doses,when cell survival rate decreased by only 5%-10%.With an increase in the radiation dose,the RBE value decreased for all studied parameters,but it remained as high as 5.Conclusion:γ,n-radiation is highly effective against CSCs.Our results explain the efficacy of neutron therapy for resistant forms of breast cancer.展开更多
文摘Exposure to toxic chemicals, especially chemotherapeutic drugs, may induce several DNA lesions, including DNA interstrand crosslinks. These crosslinks are considered toxic lesions to the dividing cells since they can induce mutations, chromosomal rearrangements, and cell death. Many DNA interstrand crosslinks lesions can be generated by platinum-based chemotherapeutic agents. Satraplatin is a novel orally administered platinum-based chemotherapeutic agent. In the present study, we investigated DNA interstrand crosslinks lesions induced by oxaliplatin and satraplatin in lymphocytes obtained from colorectal cancer patients and healthy volunteers. Satraplatin demonstrated an increase in interstrand crosslinks in a dose-dependent manner in the Comet assay (p in vitro. Here, to the best of our knowledge we report for the first time evidence of DNA double strand breaks formation as a possible molecular mechanism of action for satraplatin.
基金The work was supported by the National Research Center“Kurchatov Institute”.
文摘Aim:Cancer stem cells(CSCs)are highly resistant to chemotherapy andγ-irradiation.Neutrons have a high linear energy transfer,which can lead to extensive damage to the DNA of tumor cells and CSCs.The aim of this work was to compare the sensitivity of MCF-7 human breast adenocarcinoma cells and CSCs toγ-andγ,n-irradiation.Methods:To increase the number of CSCs,MCF-7 cells were cultured as mammospheres.γ-irradiation was carried out in a GUT-200M device(^(60)Co source)in the dose range of 1-8 Gy at a dose rate of 0.75 Gy/min.γ,n-irradiation was carried out in an IR-8 reactor in the dose range of 0.05-2 Gy at a dose rate of 0.06 Gy/min.DNA DSB formation was assessed by the level ofγH2AX foci using fluorescence microscopy and flow cytometry.CSCs were identified by flow cytometry as CD44^(+)/CD24^(-/low) cells.Results:We showed thatγ,n-irradiation induced the formation ofγH2AX foci of a larger size than didγ-irradiation and led to more severe DNA damage per 1 Gy.Moreover,γ,n-radiation was found to have a high relative biological effectiveness(RBE)as assessed by the cell survival rate,the number of CSCs in culture,and the ability of CSCs to repopulate.The highest RBE of neutron radiation was observed at low doses,when cell survival rate decreased by only 5%-10%.With an increase in the radiation dose,the RBE value decreased for all studied parameters,but it remained as high as 5.Conclusion:γ,n-radiation is highly effective against CSCs.Our results explain the efficacy of neutron therapy for resistant forms of breast cancer.
