ABSTRACT
This study observed the effects of Guiqi Yiyuan Ointment(GQYY) on the left lung subjecting to bystander effect of right lung injury induced by ~(12)C~(6+) beam in rats and decipher the underlying mechanism from NOD-like receptor protein 3(NLRP3)/apoptosis-associated speck-like protein containing a CARD(ASC)/cysteinyl aspartate specific proteinase-1(caspase-1) pathway. Wistar rats were randomized into 7 groups: blank, model, inhibitor [200 mg·kg~(-1), N-acetylcysteine(NAC)], western drug [140 mg·kg~(-1) amifostine(AMI)], and high-, medium-, and low-dose(4.8, 2.4, and 1.2 g·kg~(-1), respectively) GQYY groups. The model of bystander effect damage was established by 4 Gy ~(12)C~(6+) beam irradiation of the right lung(with the other part shielded by a lead plate). The pathological changes in the lung tissue, the level of reactive oxygen species(ROS) in the lung tissue, and the levels of superoxide dismutase(SOD) and malondialdehyde(MDA) in the serum were observed and measured in each group. Furthermore, the mRNA and protein levels of NLRP3, ASC, caspase-1, and phosphorylated nuclear factor-κB p65(p-NF-κB p65)/nuclear factor-κB p65(NF-κB p65) were determined. Compared with the blank group, the model group showed thickened alveolar wall, narrowed alveolar cavity, and presence of massive red blood cells and inflammatory infiltration in the alveolar wall and alveolar cavity. In addition, the model group showed elevated ROS levels in both left and right lungs, elevated MDA level, lowered SOD level, and up-regulated mRNA and protein levels of NLRP3, ASC, caspase-1, and p-NF-κB p65/NF-κB p65. Compared with the model group, the drug administration in all the groups reduced inflammatory cell infiltration in the lung tissue. The inhibitor group and the western drug group showed enlarged alveolar cavity, thinned interstitium, and reduced inflammation. There was a small amount of alveolar wall rupture in the high-and medium-dose GQYY groups and reduced inflammatory cell infiltration in the low dose GQYY group. Compared with the model group, drug administration lowered level of ROS in the left and right lungs, lowered the MDA level, elevated the SOD level, and down-regulated the mRNA and protein levels of NLRP3, ASC, caspase-1, and p-NF-κB p65/NF-κB p65. GQYY can effectively reduce the damage caused by radiation and bystander effect, which may be associated with the ROS-mediated NLRP3 inflammasome activation.
Subject(s)
Rats , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NF-kappa B/metabolism , Inflammasomes/metabolism , Lung Injury/genetics , Reactive Oxygen Species/metabolism , Bystander Effect , Ointments , Rats, Wistar , Lung/metabolism , Caspase 1/metabolism , RNA, Messenger , Superoxide DismutaseABSTRACT
Metabolic reprogramming refers to the phenomenon that tumor cells, in order to meet their own growth and energy needs, regulate their biological functions by changing their metabolic mode, help themselves resist external stresses, and thus enable cells to adapt to hypoxia, acid, nutrient deficiency and other microenvironments and rapidly proliferate. It was found that metabolic reprogramming could contribute to radiation resistance and it also could be induced in bystander cells which may result in radiation resistance and the cancellation. Investigation the mechanism of radiation-induced metabolic reprogramming may provide new ideas and a theoretical framework for radiation protection, radiotherapy, and radio-diagnosis. This article reviewed the research progress on the mechanism of metabolic reprogramming in the direct and bystander effects of radiation.
ABSTRACT
Radiation-induced bystander effect (RIBE) refers to that irradiated cells release signaling factors and induce responses in nonirradiated cells.In other words, it is the communication between irradiated and nonirradiated cells by intracellular signals. RIBE could influence the efficacy of tumor radiotherapy, but also has potential risk to the normal tissues outside of radiation field. Studies have found that ionizing radiation can induce the alteration of miRNA expression not only in the irradiated cells but also in adjacent nonirradiated tissues, and miRNAs may play an important role in the regulation of signaling pathways between irradiated and nonirradiated bystander cells. This article reviewed the roles of miRNAs in RIBE.
ABSTRACT
Nuclear energy is widely used in various fields such as military, medicine, scientific research, industry and agriculture.Nuclear accident may lead to radiation damage to the bodyofpractitioners. At present, the treatment of severe bone marrow radiation sickness is still not ideal.Exosomes are small vesicles with a size of 30-130 nm secreted by living cells and carry a variety of active substances including protein, RNA, DNA, which isimportant medium of intercellular communication.The contents of exosomes can be used not only as biomarkers of radiation damage, but also for the treatment of radiation damage. This article reviewsthe research progress of the application of exosomes in radiological medicine and underlying mechanisms.
ABSTRACT
Objective To investigate the role of ceramide in radiation induced bystander effect (RIBE) in vivo by irradiating Caenorhabditis elegans with proton microbeam.Methods The posterior pharynx of wide-type N2 and genetically mutated L4-staged worms was irradiated with 2 000 particles,then germ cell apoptosis and gene expression were analyzed.Results Point-fixed radiation to posterior pharynx of N2 worms significantly increased the number of apoptotic germ cells (t =9.007,P＜0.05),but not in the worms with deletion mutants of ceramide synthase (CerS) genes (hyl-1 and lagr-1) (P＞0.05).Realtime quantitative PCR assay indicated that in both N2 and lagr-1 (gk327);hyl-1 (ok976) worms,the genes of egl-1 and ced-13 in core apoptosis pathway were up-regulated after radiation to posterior pharynx,without statistical significance between these two strains (P＞0.05).The gene expression levels of hyl-1 and lagr-1 were increased in both N2 and hus-1 (op241) worms after radiation with no statistical significant difference between two strains (P＞0.05).Furthermore,radiation-induced germ cell apoptosis was increased in abl-1 (ok171) worms (t=13.241,P＜0.05),rather than in lagr-1(gk327);hyl-1(ok976);abl-1(ok171) worms (t=13.462,P＜0.05).Conclusions Ceramide is required for RIBE on germ cell apoptosis in C.elegans,and it might play function together with egl-1 and ced-13 in core apoptosis pathway and HUS-1 in DNA damage response pathway.But ceramide had antagonistic relationship with anti-apoptotic protein abl-1 in germ cell apoptosis.
ABSTRACT
Objective@# To identify the differentially expressed miRNAs in the exosomes secreted from γ-ray irradiated cells and provide new clues in disclosing the mechanisms of radiation-induced bystander effects.@*Methods@#The human bronchial epithelial cells (BEP2D) were irradiated with 60Co γ-rays, and the exosomes were collected by ultracentrifugation from the culture medium of 2 Gy-irradiated cells and non-irradiated control. The exosomes were identified by an electron microscopy. The miRNA microarray technique was used to analyze the miRNA expression profiles in the exosomes. qRT-PCR was used to verify the miRNAs expression. The functional pathways of miRNAs targeting genes were predicted by informatic analysis using the databases of TargetScan, miRanda, GO and KEGG.@*Results@#Sixteen miRNA with significantly increased expression (P<0.05) were identified in the exosomes of BEP2D cells at 4 h post-2 Gy irradiation as compared with the non-irradiated control cells, among which miR-100-5p, miR-1246, miR-29b-3p, and miR-7-5p were further confirmed to be unregulated by qRT-PCR assay (P<0.05). Meanwhile, the expression changes of above-mentioned four miRNAs were also investigated in the irradiated cells. The data indicated the expression was significantly increased at 2 h post-2 Gy irradiation for the miR-100-5p, miR-1246, miR-29b-3p in addition to miR-7-5p. However, all these four miRNAs were downregulated in the cells at 4 h post-irradiation and then gradually recovered. Bioinformatics analysis showed that the targeted genes of these differentially expressed miRNAs might participate in the biological processes and signal pathways of cell adhesion, mTOR signal pathway, chromatin modification, HR and NHEJ pathways of DNA repair and so on.@*Conclusions@# Radiation-inducible miRNAs have been identified in the exosomes from the irradiated BEP2D cells. The target genes of these miRNAs play roles in a series of important biological processes and functional pathways, which provides new clues in elucidating the mechanisms of radiation-induced bystander effects.
ABSTRACT
Objective To explore the influence of Guiqiyiyuan Ointment on the expressions of caspase-3 and caspase-9 in the lung and kidney of the rats damaged by heavy ion (12C6+) radiation-induced bystander effect.Methods The Wistar male rats were equally and randomly divided into seven groups,normal control group (NCG),radiation alone group (RAG) and Chinese medicine group (CMG),with the latter two groups being redivided into 6,12 and 24h groups according to the executing time.The Chinese medicine groups were given Guiqiyiyuan Ointment by gavage for two weeks in advance.The normal control group and the radiation alone groups were given the equal normal saline.Afterwards,the right lung of the rats in the radiation alone groups and Chinese medicine groups were radiated by 2Gy 12C6+ ion once.The rats in normal control group were not radiated.All groups of rats were executed 6,12,and 24h after radiation.The protein and mRNA expressions of caspase-3 and caspase-9 in the right lung,left lung and left kidney were examined with immunohistochemistry and Q-PCR.Results Compared with the normal control group,the mRNA expressions of caspase-3 and caspase-9 in the right lung,left lung and left kidney in the radiation alone groups obviously increased 6 and 24h after radiation.While the protein expressions of caspase-3 and caspase-9 in the radiation alone group obviously increased only 24h after radiation (P＜0.01).Compared with the radiation alone groups,the expressions of protein and mRNA ofcaspase-3 and caspase-9 were obviously down-regulated in the Chinese medicine groups (P＜0.01).Conclusion By controlling the up-regulation of the expression ofcaspase-3 and caspase-9,Guiqiyiyuan Ointment can prevent the lung and kidney cell apoptosis and alleviate the damage caused by heavy ion radiation-induced bystander effect in vivo.
ABSTRACT
Objective To investigate the mechanism of Guiqiyiyuan Ointment (GO) for preventing and treating 12C6+ beam radiation induced lung and kidney bystander effect to provide a new strategy for prevention and treatment of clinical radiation injury. Methods Sixty healthy male Wistar rats were randomly and equally divided into 3 groups: NC group, SR group (simple radiation 2ml/kg), GO group(GO 2ml/kg intragastric administration for 7 days). The right side of the lung was modeled by 12C6+beam radiation. After modeling, the rats were killed at 48h. The left lung, left and right kidney tissues were taken from the rats. The DNA methylation rate was detected by ELISA assay, pathological changes were observed by HE staining, and the expressions of Dnmt1, Dnmt3a and Dnmt3b were detected by immunohistochemistry. Results Compared with the NC group, the level of DNA methylation was decreased significantly (P<0.01), the left lung showed inflammation, no abnormal finding was seen in the left and right kidneys, and the expressions of Dnmt1, Dnmt3a and Dnmt3b were significantly increased in the SR group (P<0.01). Compared with the SR group, the level of DNA methylation was increased significantly (P<0.01), the left lung inflammation became better, and the expressions of Dnmt1, Dnmt3a and Dnmt3b were significantly decreased in the GO group (P<0.01). Dnmt1, Dnmt3a and Dnmt3b proteins were expressed in the cytoplasms of bronchial and renal tubular epithelial cells in all the groups. The NC group presented as light brown-brown staining, showing a weak positive expression, the SR group as brown-brown staining, showing astrong positive expression, and the GO group as light brown-brown staining, showing a moderate positive expression. Conclusion The GO can reduce the bystander effect caused by 12C6+ beam radiation, and its mechanism is related to improving the level of DNA methylation.
ABSTRACT
Objective To investigate the bystander effect injury to lung-heart-liver-spleen caused by 12C6+ beam radiation,and explore the prevention and treatment effect of Guiqiyiyuan ointment on the injury and its mechanism.Methods Ninety healthy male Wistar rats were randomly divided into 3 groups:NC group (normal control,normal saline 2ml/kg,n=30),SR group (simple radiation,8Gy,2ml/kg,n=30),GO group (Guiqiyiyuan ointment 11.83g/kg,radiation,8Gy,n=30).All the rats received intragastric administration for 7 days.The right side of the lung was modeled by 12C6+ beam radiation.After modeling,the rats were killed at 48h.The heart,liver and spleen were taken.The malonaldehyde (MDA),glutathione (GSH),glutathione peroxidase (GSH-Px),superoxide dismutase (SOD) contents were measured by colorimetry,DNA methylation rate was assayed by ELISA,and the expressions of Dnmt1,Dnmt3a and Dnmt3b were detected by immunohistochemistry.Results Compared with NC group,the contents of SOD,GSH and GSH-Px decreased (P＜0.01),MDA increased (P＜0.01),the level of DNA methylation decreased (P＜0.01),and the expressions of Dnmt1,Dnmt3a and Dnmt3b increased in SR group (P＜0.01).Compared with SR group,the contents of SOD,GSH and GSH-Px increased (P＜0.01),MDA decreased (P＜0.01),the level of DNA methylation increased (P＜0.01),and the expressions of Dnmt1,Dnmt3a and Dnmt3b decreased in GO group (P＜0.01).Dnmtl,Dnmt3a and Dnmt3b proteins were expressed in the cytoplasm of myocardial cells,hepatocytes and peripheral B cells of the white pulp in spleen,in all the groups.The color of NC group was light brown-brown,showing a weak positive expression.The color of SR group was brown-brown,showing a strong positive expression.The color of GO group was light brown-tan,showing a moderate positive expression.Conclusion The Guiqiyiyuan ointment can reduce the bystander effect caused by the 12C6+ beam radiation,and its mechanism is related to improving the oxidative stress reaction and the level of DNA methylation.
ABSTRACT
Tumor radiation therapy (RT)can affect the immune system.Latest studies show that appropriate RT can activate the immune system through regulating tumor microenvironment,activating immune cells and releasing danger signals,and can produce bystander or abscopal effect.With the development of clini-cal biomarkers research and clinical trials about RT combined with immunotherapy,it is expected to change the traditional pattern of tumor treatment.
ABSTRACT
Ultraviolet C (UVC) irradiation (λ: 200-280 nm) causes release of several secretory cytokines responsible for inflammation. Our objective was to investigate whether inflammatory response was also induced in bystander cells. For this purpose, the conditioned medium containing the released factors from UVC irradiated A375 cells was used in this study to evaluate the expression of inflammatory markers, such as tumour necrosis factor alpha (TNFα), nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and p38 mitogen-activated protein kinase (p38 MAPK) in its bystander cells. Inflammatory responses in bystander cells subjected to further irradiation by UVC or other damaging agent like H2O2 were also examined. It was observed that TNFα, NFκB and p38 MAPK were not induced in UVC-bystander cells, but their expression was suppressed in the UVC-bystander cells treated with UVC or H2O2. This lowering in inflammatory response might be due to smaller depletion in the reduced glutathione (GSH) content present in these treated bystander cells. The study indicated that UVC-induced bystander effect was an intrinsic protective response in cells, capable of suppressing inflammation induced in cells on exposure to damaging agents.
Subject(s)
Bystander Effect/drug effects , Bystander Effect/immunology , Bystander Effect/radiation effects , Cell Line, Tumor , Cytokines/immunology , Humans , Hydrogen Peroxide/pharmacology , Inflammation/immunology , /immunology , Radiation Dosage , Ultraviolet RaysABSTRACT
Objective To investigate the effect of SKP2 expression on radiation induced bystander effect (RIBE) of esophageal cancer cells.Methods The esophageal cancer cell lines with different SKP2 levels were applied for the study and the SKP2 expression was identified by Western blot.Micronuclei (MN) assay and DNA foci assay were used to evaluate the effect of SKP2 on RIBE.The cells were transfected with SKP2 gene or SKP2 siRNA to further verify the effect of SKP2 on RIBE.Results MN assay showed that the bystander effect induced by the cells with a high level of SKP2 was lower than that induced by the cells with a lower level of SKP2 (t =8.06,P ＜ 0.01).These results were further confirmed by the gene transfection experiments.When the expression of SKP2 was increased,RIBE was decreased (t=11.12,10.16,P ＜ 0.01).Contrarily,when the expression of SKP2 was reduced,RIBE was increased (t =8.39,8.83,P ＜ 0.01).γ-H2AX foci formation assay disclosed that when SKP2 expression in the irradiated cells increased,the repair ability of DNA damage in the bystander cells was higher than the control (t =6.85,7.10,P ＜ 0.01).With the expression of SKP2 decreased,the repair ability of DNA damage was lower than the control (t =7.66,8.47,P ＜ 0.01).Conclusions Over-expression of SKP2 inhibits RIBE of esophageal cancer cells,at least partly through regulating DNA damage repair ability.
ABSTRACT
Objective To establish an experimental model for the study of α-particle-induced bystander effect of DNA damage and investigate the characteristics of bystander DNA double-strand break (DSB).Methods The red fluorescence fusion protein of HsBrkl-RFP was used to mark the cytoplasm of one cell line to distinguish the irradiated target cells (HFS-RFP) and the non-irradiated bystander cells (HFS) in the co-culture cellular model.After α-particle irradiation,cellular DSB and its repair kinetics were analyzed by the immunofluorescence staining of γH2AX and laser confocal microscope observation.Results A bystander studying model was established by co-culturing human HFS-RFP cells with its partner HSF cells.After 0.1 Gy or 0.2 Gy α-particle irradiation,the similar kinetics of γH2AX foci production and abatement were observed in both irradiated HFS-RFP cells and non-irradiated bystander HFS cells,in which the highest level of γH2AX foci was detected at 1 h post-irradiation.The second peak of γH2AX foci formation appeared at 8 h post-irradiation,which possibly indicates the occurrence of secondary DSB.However,the production of secondary DSB in the bystander cells was weaker than that in the irradiated cells.Conclusions The cell co-culture model can be used for bystander effect investigation.Bystander DSB can be effectively induce by irradiation and the secondary breakage of DNA DSB in the bystander cells may relative to the consequential biochemical processing of clustered DNA damage.
ABSTRACT
Bystander effect is the communication of signals from irradiated to unexposed neighboring cells which is often mediated through factors released from irradiated cells. We have attempted to investigate whether UV-bystander phenomenon can modulate the sensitivity of A375 cells and its mechanism. For this purpose, the conditioned medium from UVC-irradiated cells, which contained these released factors, was used to treat non-exposed cells. These cells were then subsequently treated with UVC or another genotoxicant H2O2. Cell viability was determined by Trypan blue-exclusion assay, DNA damage by flow cytometry analysis, ROS production by flow cytometry and microscopic analysis. Lipid peroxidation and antioxidant defense were assayed biochemically. Our findings revealed that exposure of non-irradiated cells to these factors induced increased in SOD and catalase activities which reverted to normal levels by 8 h. During this period, the released factors-treated cells were resistant to killing by UVC or H2O2 and induced DNA damage and lipid peroxidation were also lowered. This protection from cell killing was not present 8 h after exposure to these released factors. Our results suggested UV-bystander effect increased viability of cells through induction of antioxidant defense. This indicated UV-bystander phenomenon triggers protective response in cells.
Subject(s)
Antioxidants/metabolism , Bystander Effect/radiation effects , Lipid Peroxidation , DNA Damage/radiation effects , Cells/radiation effects , Rod Cell Outer Segment/radiation effects , Mammals , Ultraviolet RaysABSTRACT
Adipose-derived stem cells (ASCs) are believed to have potential use for treating many illnesses. Most cells, including ASCs, are generally cultured in medium containing fetal bovine serum (FBS). However, FBS, which could induce an immune response or infection, is not recommended for clinical applications. In the present study, we evaluated the morphology, proliferation rate, and characterization of rabbit ASCs grown in medium containing autologous serum (AS) and compared these cells to ones cultured with FBS. Morphological changes were monitored by microscopy and flow cytometry. Proliferation rates were assessed with cell counting and ASC phenotypes were characterized by flow cytometry using representative surface markers (CD44 and CD45). Expression of epidermal growth factor, brain-derived neurotrophic factor, and vascular endothelial growth factor was measured by reverse transcription-polymerase chain reaction. Results of our study showed that ASCs had a greater expansion rate in AS without developing morphological heterogeneity than cells grown in FBS. AS-cultured ASCs expressed representative growth factors, CD44 but not CD45, similar to cells cultured in FBS. Expression levels of some growth factors were different between AS and FBS. In conclusion, our findings indicated that AS could potentially be used as a culture medium supplement for the expansion of autologous ASCs.
Subject(s)
Brain-Derived Neurotrophic Factor , Bystander Effect , Cell Count , Epidermal Growth Factor , Flow Cytometry , Intercellular Signaling Peptides and Proteins , Microscopy , Phenotype , Population Characteristics , Stem Cells , Vascular Endothelial Growth Factor AABSTRACT
Objective: To study the changes of PTEN gene expression in radiation-induced bystander cells. Methods: The irradiated cells and non-irradiated cells were co-cultured in a ratio of 1:1. The culture medium of irradiated cells was used to culture non-irradiated cells to create two bystander cell models. The expression of PTEN mRNA and protein in the bystander cells, irradiated cells, non-irradiated cells was compared. Results: The protein expression of PTEN in the irradiated cells was negatively associated with the irradiation dose. The down-regulation degree of PTEN protein was related to the different treatments of cells. The most prominent down-regulation was found in the bystander cells cultured with medium of irradiated cells. The down-regulation of PTEN protein in the two kinds of bystander cells was more severe than that in the irradiated cells (P<0.01). Conclusion: PTEN protein expression can be influenced by low dose radiation and the bystander effect of radiation.
ABSTRACT
Nowadays, tumor is one of the most challenging human health diseases, which oblige human tirelessly to studied for the tumor.Gene therapy is a promising treatment in oncotherapies. Suicide gene therapy is the most widely researched among gene therapies. At the same time, bystander effect take important role in the mechanism of suicide gene therapy. Therefore, more researchers devote themselves to studyinghow enhance the bystander effect in order to improve the effect of suicide gene therapy. This article reviewed in short how to augment bystander effect of suicide gene therapy against cancer.
ABSTRACT
Objective To investigate radiation induced bystander effect and its mechanism on hepatoma HepG2 cells under hypoxia condition. Methods Non-irradiated bystander hepatoma cells were co-cultured with irradiated cells or treated with the conditioned medium (CM) from irradiated cells, then micronuclei (MN) were measured for both irradiated cells and bystander cells. Results The MN yield of irradiated HepG2 cells under hypoxic condition was significantly lower than that under normoxia, the oxygen enhancement ratio of HepG2 cells of MN was 1.6. For both hypoxic and normoxic condition, the MN yield of bystander cells were obviously enhanced to a similar high level after co-culturing with irradiated cells or with CM treatment, and it also correlated with the irradiation dose. When the hypoxic HepG2 cells were treated with either DMSO, a scavenger of reactive oxygen species (ROS), or aminognanidine, an iNOS inhibitor, the yield of bystander MN was partly diminished, and the reducing rate of DMSO was 42.2%-46.7 %, the reducing rate of aminognanidine was 42 %. Conclusion ROS, NO and their downstream signal facets are involved in the radiation induced bystander effect of hypoxic HepG2 cells.
ABSTRACT
Objective To study the bystander effects and associated mechanisms through irradiated conditioned medium(1CM). Methods Natural kilhr(NK) cells were obtained from peripheral blood samples. ICM irradiated with different doses of 60Coγ-rays was used for culturing K562 cell strain. The degree of injury of K562cells by activated NK cells was observed, as well as the apoptosis frequency of K562 cell was investigated. Results Severe injury was induced in K562 cells cultured in ICM than the control (sham-irradiated) as shown by increased sensitivity to NK cells (P < 0.05). The apoptosis frequency of K562 cell was increased significantly compared with the control cells (P < 0.05). Conclusions The bystander effect induced by irradiation is existent. ICM can trigger the bystander effect on K562 cell strains.
ABSTRACT
Objective To investigate the expression of FHIT gene in the 60Co gamma-ray irradiated human lymphocytoblast(AHH-1) cell and the bystander effect cell,and to explore the function of FHIT gene in the bystander effect of ionizing radiation.Method Preparation of bystander effect cell model:after irradiated with different dose of 60Co gamma-ray(0,2,5 Gy),the directly irradiated AHH-1 ceils were collected immediately by centfifugation and co-cultivated with non-irradiated cells in Transwell.forming the bystander effect group P1.In addition,some culture media supernatant of direcfly irradiated cells were transfefred to the non- irradiated cells culture medium,forming the group P2.Then cells were collected at 0,6,12,and 24 h after irradiation and the total RNA and protein were extracted.RT-PcR and Western blot were performed to determine the FHIT mRNA and protein level.respectively.Flow cytometry assay and cell counting were conducted to detect the alteration of cell cycle and cell proliferation,respectively at 0,24 h after irradiation.Results The mRNA level of FHIT gene among control cells,directly irradiated cells and bystander cells showed no obvious difference. while the FHIT protein level of the directly irradiated ceils and bystander cells was siguificandy down-regulated compared with the control cells(F=102.45,P<0.001).Moreover,the directly irradiated cells and bystander cells showed significant G2 phase arrest and obviously inhibited the proliferation ability.Conclusions 2 and 5 Gy of 60Co γ-ray irradiated AHH-1 cells can result in down regulation of the FHIT protein expression,which suggests that FHIT gene is involved in the process of bvstander effect induced by irradiation.