Objective To investigate the mechanism of malignant transformation in human bronchial epithelial cell line BEP2D exposed to α-particles.Methods The levels of intracellular ROS and malonaldehyde (MDA) in BEP2D,RH22 (passage 22 of α-particle-irradiated BEP2D cells) and BERP35T-1 cells (derived from nude mice bearing malignant transformed cells generated from the passage 35 of α-particle-irradiated BEP2D cells) were assayed with DCFH-DA and MDA kit,respectively.The expressions of 8-OH-dG and γ-H2AX in BEP2D,RH23 (passage 23 of α-particle-irradiated BEP2D cells)and BERP35T-1 cells were also measured with immunocytochemistry and immunofluorescence staining.Results Compared to BEP2D cells,the levels of ROS ( t =4.30 and 3.94,P ＜ 0.05 ) and MDA ( t =4.89 and 15.10,P ＜0.05) increased in RH22 and BERP35T-1 cells.The expressions of 8-OH-dG (t =3.80 and 2.92,P ＜ 0.05 ) and γ-H2AX ( t =7.61 and 12.67,P ＜ 0.05 ) in RH23 and BERP35T-1 cells were also higher than those in BEP2D cells.Conclusions Oxidative stress induces lipid peroxidation and DNA damage leading to genomic instability,which could contribute to cellular malignant transforming process in the human bronchial epithelial cell line BEP2D with α-particle exposure.

Objective To study the effect of thorium and rare earth mixed dust on chromosome aberrations in the lymphocytes of occupational exposed worker8.Methods Analyses of unstable chromosome aberrations on 53 occupational exposed worker8 and 58 control workers were carried out by the conventional Giemsa staining method.Fluorescence in situ hybridization method Wills performed to analyze the chromosome stable aberrations on 10 occupational exposed workers and 10 control workers.Results The frequencies of chromosomal aberration cells,dicentfics plus rings,total aberrations in exposed workers were significantly higher than those in controls.No significant difference was found in the frequency of acentric aberrations between exposed and non-exposed workers.No significant difference was found in the frequency of translocations between exposed and non-exposed workers.Conclusions Chronically occupational exposure to thorium and rare earthmixed dust can increase the induction of unstable chromosome aberration,but the increase of stable chromosome aberrations(translocation)can not be observed.

Objective To investigate the effect of nicotinic acetylcholine receptor αt7 (a7nAChR) subunit gene on liver inflammation in mice with nonalcoholic steatohepatitis (NASH) and related mechanisms.Methods C57BL/6J mice and α7nAChR gene knockout mice were fed for 24 weeks to establish the NASH model,and the mice were sacrificed to isolate and culture the primary liver macrophages.After the treatment with nicotine and endotoxin,ELISA was used to measure the levels of the inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in supematant;indirect immunofluorescence assay and Western blot were used to observe the effect on the NF-κB signaling pathway,and quantitative PCR was used to measure the mRNA expression of Toll-like receptor-4 (TLR-4) in macrophages.An analysis of variance was used for comparison of means between multiple groups.Results The results of ELISA showed that compared with the endotoxin+nicotine group of C57 NASH mice,the endotoxin+nicotine group of gene knockout NASH mice had significantly higher levels of IL-6 and TNF-α in supernatant (IL-6:1 599±65 pg/ml vs 1 465±45 pg/ml,P ＜ 0.05;TNF-α:1 567±66 pg/ml vs 1 433±50 pg/ml,P ＜ 0.05).The results of Western blot showed that compared with the endotoxin+nicotine group of C57 NASH mice,the endotoxin+nicotine group of gene knockout NASH mice had significantly higher relative protein expression of phosphorylated NF-κB and TLR-4 (NF-κB:69 425±600 vs 51 1334200,P ＜ 0.05;TLR-4:93 387±684 vs 64 198±630,P ＜ 0.05).The results of indirect immunofluorescence assay showed that the endotoxin+nicotine group of gene knockout NASH mice had a significantly higher fluorescence intensity of NF-κB than the endotoxin+nicotine group of C57 NASH mice.The results of PCR showed that the endotoxin+nicotine group of gene knockout NASH mice had significantly higher relative mRNA expression of TLR-4 than the endotoxin+nicotine group of C57 NASH mice (4.13±0.13 vs 2.93±0.14,P ＜ 0.05).Conclusion The α7nAChR gene knockout can aggravate the degree of inflammatory reaction in NASH,and its mechanism may be related to the fact that the NF-κB signaling pathway cannot be inhibited,which aggravates inflammatory reaction.