| Life could be threatened by a lot physical or chemical stresses in the environment, including ultraviolet,ionizing radiation and cigarette smokes.Such stress can cause damage,especially DNA damage in cells,which is called genotoxicity.Due to the extensive and insightful research about DNA damage in recent years,we have now acquired a rather large body of knowledge about the mechanisms involved in DNA damage induction and signaling.However,many questions remain unanswered,which warrant further detailed investigation.There have been controversies about whether heat shock could induce DNA damage.While we previously found heat shock could not induceγH2AX foci formation,which is regarded as a marker of DNA double strand breaks,Takahashi et al suggested otherwise.In order to clarify this discrepancy,the effects of five different heating methods onγH2AX foci formation were examined.We found that the cytotoxicity effects of different heating methods varied differently,and different cell types showed different heat shock responses.It was found that during a 24 h period, heating at 42℃for 30 min did not cause significant loss of cell viability,while 45℃caused various degrees of decrease in cell viability.The ability of these five methods to induceγH2AX foci was quite distinct,with only heat block inducedγH2AX foci at both 42℃and 45℃in both FL and CHL cells.The two cell types also respond differently to the different heating methods,with CHL being more sensitive to heat shock.However,expression ofγH2AX may not be used as a surrogate of cell killing.Cisplatin is an effective anti-cancer drug widely used in clinical treatment of reproductive system cancers as well as head and neck cancers;however,the underlying mechanisms are not fully clear yet.Systems biology approaches provide us new platforms to conduct study at whole genome or proteome level.Several groups have used proteomic technologies to explore the anti-cancer mechanisms of cisplatin,and identified some responsive proteins.However,as DNA is the primary target of cisplatin,and many cellular events induced by cisplatin took place in nucleus,we analyzed the nuclear proteome expression pattern after cisplatin treatment.A total of 19 proteins were eventually successfully identified among those differentially expressed proteins.These include nuclear lamina proteins,mRNA processing-related proteins,cell cycle-related proteins and synthesis-related enzymes,all of which were involved in basal metabolism and biological process in cells.The changed expression pattern of these proteins were further validated by Western blot or immunofluorescent microscopy,and cisplatin-induced alternative splicing was confirmed by RT-PCR analysis of Fas gene transcripts.Nanotechnology is a fast growing area,and nanomaterials have great application potentials due to their unique physical and chemical properties.However,the potential toxic effects of the nanomaterials are not clear,and it has attracted a lot attention recently.Quantum dots(QD) are semi-conductive nanomaterials that can be used for cell imaging.In this study,we also evaluated the potential toxic effects of quantum dots using proteomic approach.Results of cell survival test showed that poly(ethyleneglycol)-coated CdSe/ZnS core/shell quantum dots did not significantly affect the cell viability of human skin fibrobalsts(HSF).By proteomic analysis,a total of 21 proteins were found differentially expressed after 8 nM and 80 nM PEG-QD440 and PEG-QD680 treatment.MS analysis identified 5 proteins,including two zinc finger proteins,two keratins and Peroxiredoxin-2.Since 21 proteins only count for about 0.5%of the total proteins in HSF cells,it indicated that PEG-QD may not elicit significant adverse effects in cells.PEG-Qdots could be a promising agent in biological and medical applications.
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