ABSTRACT
Objective To investigate the effect of low-dose arsenious acid solution (As(III)) combined with total particulate matter (TPM) from cigarette smoke on cellular oxidative stress in human lung cancer cell line A549 cells. Methods A549 cells were divided into four groups: negative control group (0.75% DMSO), low dose As(III) group (0.88% μg/mL, 75% DMSO), cigarette smoke TPM group (75 μg/mL), and combined exposure group (75 μg/mL TPM, 0.88 μg/mL As (III)). After 24 hours' exposure, the superoxide dismutase (SOD) level in cell culture medium and intracellular 8-hydroxy-2-deoxyguanosine (8-OHdG) content were detected by ELISA, and intracellular reactive oxygen species (ROS) level was detected by fluorescent probe DCFH-DA. 2×2 factorial design was used to evaluate the interaction. Results Compared with the control group, the level of SOD in the combined exposure group was significantly increased (P<0.05). In addition, the ROS content in the combined exposure group and TPM alone group was significantly increased (P<0.05). The levels of 8-OHdG in the combined exposure group and low-dose As(III) treated group were significantly higher than those in the control group(P<0.05). The results of the factorial analysis showed that low-dose As(III) and TPM had interaction on SOD levels, ROS and 8-OHdG contents in A549 cells. The effects on SOD and ROS were synergistic, while the effect on 8-OHdG was antagonistic. Conclusion Low-dose arsenious acid solution As(III) and TPM in cigarette smoke have interaction on oxidative stress in A549 cells.
ABSTRACT
In order to understand the current development of cell transformation assay (CTA) and its application in the evaluation of cigarette smoke carcinogenesis, the relevant literatures were analyzed and combed from these two aspects. CTA can evaluate the carcinogenicity of various genotoxic and non-genotoxic carcinogens in a short period of time, and has a strong consistency with the results of animal carcinogenic test. After malignant transformation, the cells show changes in cell morphology, immortalization of cells, disappearance of cell-cell contact inhibition, and the ability to form tumors when injected into animals. The identification methods of transformed cells include transformed cell focus count, agglutination test, soft agar culture and inoculation of nude mice, etc. At present, BALB/c 3T3 cells, Bhas 42 cells and SHE cells are the most widely used cells for CTA. Cigarette smoke is a complex aerosol containing a variety of non-genetic carcinogenic chemicals. Cell transformation tests are often used as an in vitro alternative method to evaluate the carcinogenic effects of cigarette smoke, which is different from the short-term genetic toxicity test. It simulates the long-term state of human smoking induced malignant transformation of cells, through the long-term exposure of cells for several decades, which is closer to the occurrence of cancer caused by human smoking. Therefore, CTA can evaluate the carcinogenicity of cigarette smoke and other tobacco products.
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Objective To explore the effect on metabolism of glucose and lipids, potential toxicity mechanism and possible biomarker candidates by analyzing urine metabonome changes of rats after oral administration of polychlorinated biphenyl congeners( PCBs) and high fat diet alone or in combination.Methods Male SD rats were divided randomly into control group,high fat diet group, PCBs group and combination group of PCBs and high fat diet.Urine samples were collected after 6-week treatment, 1 H NMR spectra were performed and analyzed by principal component analysis ( PCA) . Results The PCA scores plot of urine 1 H NMR data showed that the combined group could be easily distinguished from the other three groups, suggesting great difference in metabolism.The loading plot of the PCA revealed significant increase in the levels of lactate, glucose, creatine, 2-hydroxy-isovaleric acid and reduction in the levels of citrate, succinate, taurine, hippurate and trimethylamine oxide ( TMAO) in the combined exposure group after six-week exposure.Conclusion The altered levels of metabolites induced by combined exposure of PCBs and high fat diet may be related to the injury to mitochondrial function, reduction of energy metabolism in tricarboxylic acid cycle (TAC).These effects possibly lead to perturbations in the metabolism of glucose, lipid and amino acids.The altered metabolites may be considered biomarker candidates of toxicity induced by exposure to PCBs and high fat diet.
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OBJECTIVE To investigate the role of gonadotropin-releasing hormone (GnRH) in es-tradiol(E2 ) induced advance of puberty onset in rats. METHODS Postnatal day 18 SD rats were given a daily intragastric administration of corn oil or E2(50 μg.kg-1 ) for consecutive 5 d. The day of vaginal opening (VO), pathological changes in ovary and protein expression levels of GnRH, G protein-coupled receptor 54 ( GPR54) and phospholipase C ( PLC) in hypothalamus were observed. RESULTS As compared to corn oil controll group, VO was advanced by about 12.2 d, corpus luteum was observed in the ovary section, and the protein expression levels of GnRH,GPR54 and PLC in hypothalamus were significantly increased by 47%, 55% and 56% in E2 group, respectively. CONCLUSION E2 induced onset of puberty advance may be closely related to regulation of the expression of GnRH, GPR54 and PLC in hypothalamus.