In the early 1950s,China′s modern industry and national defense developed rapidly. While toxicological research,represented by occupational toxicology,radiological toxicology and military toxicology,was initiated. Along with the expansion of industrial and agricultural activities and production, high- speed economic development,and the changes of the environment and lifestyles,the objects and content of toxicological research have also been expanded. Subdisciplines of toxicology have kept emerging,and an integrated toxicological discipline and research system has been established. Toxi?cological research has become an active area in China. Toxicological publications from China have accounted for about 10% to 20% of total international toxicological research papers in the recent ten years. Toxicologists in China have paid much attention to the toxicities and biological safety of new materials and emerging pollutants,such as nanomaterials and fine particles in the air. Some toxicological research was discussed in this paper.

Objective To determine the Golgi dispersal in radiation damaged cells and the protective effect of vanillin derivatives.Methods Immunofluorescence, cell cycle analysis of flow-cytometry,Western blot,and clone formation were used.Results Immunofluorescence observation showed that the Golgi dispersal caused by 2 Gy 60 Coγ-ray was significantly increased in a dose-dependent manner in the range of 4-10 Gy as was demonstrated by the fact that the Golgi area was significantly increased. When the irradiated cells were treated with the radioprotective agent VND3207, a vanillin derivative,the Golgi dispersal induced by radiation was significantly reduced.The radiation-induced Golgi dispersal was also displayed in a pattern of time-course after irradiation in the HeLa cells, and persisted at least to 36 h post-irradiation. Cell cycle test results indicated that the Golgi dispersal was not associated with the G2/M arrest triggered by radiation-induced DNA damage response.VND3207 could promote cell survival by plate colony formation assay.Conclusion The Golgi dispersal can be caused byγ-ray irradiation in a dose-and time-dependent manner, and VND3207 can provide a good protection against radiation injury associated with inhibited Golgi dispersal.

Regulation of gene expression is one of the most importa nt responses of cells to DNA damage induced by radiation. A novel expressed seq u ence tag (EST) fragment had been cloned from human embryo lung cells induced by 50cGy radiation and named RIG1. To clone the full-length cDNA of RIG1, a non-c loned cDNA library of human embryo lung cells induced by low dose irradiation ha d been established. This library was used as template in enchanced nest RACE PCR and biotin-labeled probe was used for further purification. The 3′ flanking s equence of this EST was cloned and sequenced with this set of technology. It was illuminated by homology analysis that this 3′ flanking sequence and the origin al EST are well aligned with a BAC clone of 20th chromosome and the predic ted exons sequence of this chromosome is well consisten ce with the real EST. Thus the RIG1 can be roughly located in 20th chromos ome. By use of the exons sequence predicted from chromosome sequence by GENSCA N, full-length of RIG1 gene has been cloned. Chromosome location of RIG1 gene i s further determined by this successful verification of Bioinformatics predictio n by experiment. By the same step, genome sequence of RIG1 has been determined. Therefore,by the combined use of Bioinformatics analysis，the full-length cDNA sequence and genome sequence of RIG1 gene are obtained and the predicted protei n sequence is determined.

Objective To evaluate the radiosensitization and mechanism of DNA-dependent protein kinase catalytic subunit inhibitor NU7026 on HCT116 colorectal cancer stem cells.Methods The flow cytometry was used to determine the sub-population of cancer stem cells with the markers CD133/ CD44.The cells were divided into four groups:control group,20 μmol/L NU7926 group,2 Gy irradiation group,and 20 μmol/L NU7026 combined with 2 Gy irradiation group.Cell proliferation and survival were evaluated by colony-formation experiment.Flow cytometry was used to analyze the cell cycle distribution and apoptosis induction.γ-H2AX foci were detected with immune-fluorescence staining analysis by a laser confocal microscopy for investiating the DNA double-strand break repair.Results The flow cytometric data of CD133 +/CD44 + positive cells indicated that the sub-population of cancer stem cell (CSC) took the ratio of (88.14 ± 0.47)％ of the cultured HCT116 cells.The colony-formation efficiency of HCT116 cells was (84.75 ± 1.35) ％ in serum-free mediums in vitro culture.Compared to 2 Gy irradiation alone group,the NU7026 combined with 2 Gy irradiation group had a lower cell colony-forming ratio (t =7.21,P ＜0.01) and a lower survival ratio (t =7.22,P ＜ 0.01).The proportion of CSCs sub-population increased at 48 h post-2 Gy irradiation,suggesting that HCT116 CSCs was more resistant to ionizing radiation.Importantly,NU7026 largely decreased the proportion of CSCs sub-population in 2 Gy-irradiated cells.The difference of CSC proportion between 2 Gy irradiation alone group and 2 Gy combined with NU7026 treatment group was statistically significant (t =9.55,P ＜ 0.01).In addition,the group of NU7026 combined with 2 Gy irradiation had a higher ratio of G2/M arrest 24 h post-irradiation (t =7.67,P ＜ 0.01) and an increased induction of cell early apoptosis (t =8.24,P ＜ 0.05).48 h post irradiation as compared to 2 Gy irradiation alone group.NU7026 treatment significantly inhibited the cellular capacity of repairing DNA double-strand breaks induced by γ-ray irradiation.The γ-H2AX foci of the combined treatments group were much higher than that of 2 Gy irradiation alone group at 2,4,8,24 h postirradiation (t=19.58,11.95,7.01,9.45,P＜0.01).Conclusions DNA-dependent protein kinase catalytic subunit inhibitor NU7026 can significantly sensitize the cancer stem cells of colorectal carcinoma HCT116 cells to γ-ray irradiation.Multiple mechanisms are involved in the radiosensitization effect of NU7026,including DNA repair inhibition,elongation of G2/M arrest,and increase of radiation-induced apoptosis.

Objective To investigate the effect of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) on autophagy induction by ionizing radiation ( IR ) .Methods The cell model of knocking-down DNA-PKcs expression was constructed by transfecting HeLa cells with a pSicoR-based lentivirus vector expressing DNA-PKcs specific shRNA .Cellular growth activity and radiosensitivity were detected by cell countingkit ( CCK)-8 assay.The expression of autophagy related proteins was detected by Western blotting hybridization .Autophagy was also detected by monitoring the autophagic marker green fluorescere protein ( GFP )-light chain 3 ( LC3 ) puncta per cell under an immunofluorescent microscope .Results A cellular model of knocking-down DNA-PKcs expression was successfully generated by transfecting the specific shRNA against DNA-PKcs.Depression of DNA-PKcs significantly decreased the growth activity of HeLa cells and increased the cellular sensitivity to ionizing radiation .Both the expression changes of P 62 and LC3 proteins and immunofluorescent GFP-LC3 puncta observation indicated that knocking-down DNA-PKcs prompted the induction of autophagy by ionizing radiation . Moreover, inactivation of DNA-PKcs led to a decreased phosphorylation of mammalian target of sirolimus ( Rapamycin, RAPA) ( mTOR) at S2481 site.Conclusion Depression of DNA-PKcs expression prompts the induction of autophagy by IR and cellular radiosensitivity .mTOR signaling may be involved in the regulation of autophagy processing by DNA-PKcs.

Objective To comprehensively analyze the effect of low-dose radiation on the lens of the eye of radiation workers.Methods The papers dealing with the relationship between occupational radiation exposure and the lens of the eye were collected by retrieving documents of the domestic and foreign medical information databases with references to other papers.There were 28 papers finalized with 17 608 workers included in the Meta-analysis.Stata12.0 was used for Meta-analysis,Q-test and I2 statistic for heterogeneity test,and funnel regression method,Begg's rank method and Egger's regression method for publication bias.Results The pooling odds ratio (OR) opacity in radiation workers were 2.51 (2.01,3.13),4.03 (2.77,5.85),respectively.Conclusions Low-dose radiation may lead to negative impact on ocular lens under the current occupational protection conditions.The proportion of posterior subcapsular opacity in radiation-related cataract is higher than that in age-related cataract.It is important to strengthen radiation protection of ocular lens.

Objective To quantitatively investigate the effect of low-dose ionizing radiation on the frequencies of chromosome aberrations and micronucleus-containing cells of radiation workers.Methods Nine electronic databases were systematically searched on the basis of the published studies evaluating the effects of low-dose ionizing radiation on the frequencies of chromosome aberrations and micronucleuscontaining cells.Of the 195 studies searched,21 studies were identified with a total of 1 970 626 cells under studying.Cochrane' s Q and I2 statistics were used to evaluate heterogeneity among studies and pooling odds ratio (OR) with 95％ confidence intervals (CI) were calculated using random-effect models or fixed-effect models,and publication bias were also calculated.Meta-analysis was performed using Stata 12.0.Results The pooling OR of chromosome-type aberrations [OR =3.03 (2.59,3.56)],dicentric plus centric rings [OR =4.12 (2.99,5.67)],translocations [OR =2.73 (1.67,4.46)],micronucleuscontaining cells [OR =1.70 (1.40-2.06)] were higher for radiation workers when compared with control group.Conclusions The frequencies of chromosome aberrations and micronucleus cell of peripheral lymphocytes are significantly high in radiation workers who were occupationally exposed to low-dose ionizing radiation.It should be noted that the radiation protection of radiological workers be enhanced.

Objective To understand the variation of the DNA double-strand break rejoining capacity among different cultured cancer cell lines and the primary cancer cells from brain cancer patients,and to explore the predictor of radiotherapy responses of cancers. Methods DNA double-strand breaks (DSBs) were induced by 60Co γ-irradiation. Pulsed-field gel electrophoresis was used to analyze the initial production and rejoining of DNA DSBs. Radiosensitivity was determined by in vitro assay of clonogenic-forming capacity. Results A wide variation of radiosensitivity, e.g. The survival parameter of D0 varied from 0.65 to 2.15 Gy, was displayed among the eight cell lines derived from different type of cancers. Although differential level of initial DNA DSBs induced by 20 Gy γ-rays was observed among various cell lines, it was not correlated with the radiosensitivity. The deficiency of DNA DSB rejoining in radiosensitive cell lines was shown either in the early rapid-rejoining phase (SX-10 cells) or in the late slow-rejoining phase (A2780 cells). A significant relationship was observed between the residual level of DNA DSBs measured at 2 h post-20 Gy irradiation and the cellular radioseusitivity (D0 or SF2). The kinetic curves of rejoining DNA DSBs in the primary human brain tumor cells indicated a variation on DSB rejoining capacity among different individual tumor. The residual level of DNA DSBs after 2 h of rejoining post 20 Gy irradiation in primary human brain tumor cells is compatible to the results obtained in vitro culture cancer cell lines. Conclusions The residual level of DNA DSBs is correlated with radioresistance of cancer cells, and the residual DNA damage is a useful parameter in predicting the response of tumor tissue to radiotherapy.

Objective To investigate the effects of a recombinant antisense adeno virus for epidermal growth factor receptor (EGFR) combined with irradiation on b reast cancer cells.Methods Human EGFR cDNA fragment was subcloned in the oppos ite orientation to the cytomegaloviral promoter and inserted into a E1/E3-delet e d type 5 adenoviral vector to obtain AdE5 construct which expresses EGFR antisen se RNA. Combined with ?-ray irradiation, its effects on clonogenicity and cell cycle phase distribution were studied in a human breast cancer line MDA-MB-231 . Results EGFR protein expression was dramatically inhibited in MDA-MB-231 cell s after AdE5 infection. The post-irradiation clonogenicity was reduced by AdE5 in a viral and irradiation dose-dependent manner. Further cytometric analysis show e d that AdE5 infection at a?MOI of 300?pfu/cell induced a cell cycle progre ssion from radio-resistant G 0+G 1 phases to radiosensitive G 2+M phases, resultin g in a synergistic effect after combination of these two treatments. Conclusions The t ransduction of EGFR antisense RNA by adenoviral vector is effective for antisens e strategy targeting EGFR, and increases the cell-killing effect of ionizing radiation on breast cancer cells.

Objective To investigate the expression of radiation-induced IER5 protein and screen its potential interaction proteins that may participate in DNA repair process.Methods HeLa cells were irradiated with 4 Gy ionizing radiation.IER5 protein expression in whole cell lysate and in nuclear fraction were detected by Western blot at different timepoints after irradiation.3 × Flag-IER5 pCMV plasmid was constrcuted and the Flag tagged-IER5 expression was verified by Western blot.293T cells were transfected with 3 × Flag-IER5 pCMV plasmid.After irradiation the cells were collected and proteins were extracted.The IER5 interaction proteins were purified using immunoprecipitation and separated by 12％ SDS-polyacrylamide gel electrophoresis.Then the binding proteins were cut from the gel and analyzed by Mass spectrometry.Results The expression of IER5 protein began to increase 4 hour post-irradiation and its peak level was observed at 12 hour post-irradiation,and it lasted until 48 hour after irradiation.The expression level of IER5 protein in whole cell lysate and nuclear fraction were both increased.With the mass spectrometry analysis,a total of 347 proteins and 256 proteins were identified in irradiated and nonirradiated groups,respectively.Fourty one differential proteins were obtained,where 10 proteins were associated with DNA metabolic process and DNA rapair in the irradiated group and the poly(ADP-ribose) polymerase 1 (PARP1) protein was further confirmed by Western blot.Conclusions IER5 protein is an DNA damage related protein,and it may participate in DNA repair process.