Benzo(a)pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) that is easily introduced to humans via consumption of grilled or smoked meat. BaP causes harmful oxidative effects on cell development, growth and survival through an increase in membrane lipid peroxidation, oxidative DNA damage and mutagenesis. Therefore, the present study was conducted to evaluate the synergistic effects of BaP on oxidative stress in hepatic tumors. In this study, we established a hepatic tumor model by injecting rat hepatoma N1-S1 cells into healthy rats. Changes in the abundance of heat shock proteins (HSPs), antioxidant enzymes and pro-inflammatory cytokines were then investigated by western blot analysis. In addition, we examined changes in oxidative stress levels. Injection of N1-S1 cells or concomitant injection of BaP and N1-S1 cells resulted in the formation of hepatic tumors at the injection site. Evaluation of rat plasma reveals that hepatic tumors induced by BaP and N1-S1 cells expresses higher levels of Hsp27, superoxide dismutase (SOD), and tumor necrosis factor-alpha (TNF-alpha) when compared to those induced by N1-S1 cells only. The collective results of this study suggest that BaP exerts synergistic effects on the expression of HSP, cytokines and antioxidant enzymes in hepatic tumors induced by rat hepatoma N1-S1 cells.
Animals ; Antioxidants/*metabolism ; Benzo(a)pyrene/*pharmacology ; Carcinoma, Hepatocellular/metabolism/pathology ; Cell Line, Tumor/*drug effects ; Cytokines/*metabolism ; Heat-Shock Proteins/*metabolism ; Humans ; Liver Neoplasms/*enzymology/*metabolism/pathology ; Male ; Neoplasms, Experimental/metabolism/pathology ; Oxidative Stress/drug effects ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: The purpose of this study was to evaluate the levels of DNA damage in human lymphocytes caused by smoking and other lifestyle factors. METHODS: The study population consisted of 173 normal healthy male adults from 21 to 59 years old. The demographic and lifestyle variables were obtained from administered questionnaires. The level of lymphocytic DNA damage in the peripheral blood was evaluated by the Comet assay. Statistical analyses were done by general linear model analysis and Dunnett's multiple comparison. RESULTS: The difference in DNA damage between smokers and non-smokers was statistically significant. The means for the Tail%DNA were found to be 10.48 in the current smokers and 9.60 in the non-smokers (p<0.05). The tail moment means were 1.58 and 1.45 (p<0.05) for the current smokers and non-smokers, respectively. The number of cigarettes smoked per day did not result in a significant difference in the level of DNA damage among the smokers. Other lifestyle factors such as age, and drinking and exercise habits were not related to DNA damage. CONCLUSIONS: The DNA damage in the lymphocytes of smokers was found to be significantly higher than that for non-smokers. However, the number of cigarettes smoked per day was not related to DNA damage. Further study is needed to evaluate the relationship between the amount of smoking and level of damage to DNA. In addition, the status of DNA repair activities should be assessed.
Smoking/*adverse effects ; Risk-Taking ; Middle Aged ; Male ; Lymphocytes/*pathology ; Linear Models ; Life Style ; Korea/epidemiology ; Humans ; DNA Damage/*physiology ; Comet Assay ; Case-Control Studies ; Adult

In this study, we investigated the effects of PAHs and dioxin on mRNA and plasma protein expression using genomic and proteomic analysis for automobile emission inspectors and waste incineration workers. About 54 workers from automobile emission inspection offices, 31 workers from waste incinerating company and 84 unexposed healthy subjects were enrolled in this study. Urine and air samples were collected and analyzed by HPLC and GC/MS. Comet assays were carried out to evaluate any DNA damage in mononuclear and polynuclear cells. A significant difference in Olive tail moments in mononuclear cells was observed between exposed and control subjects (P <0.0001). To examine the differences of the gene expression profile in automobile emission inspectors and waste incineration workers, radioactive complementary DNA microarrays were used to evaluate changes in the expression of 1,152 total genes. The gene expression profiles showed that 11 genes were up-regulated and 4 genes were down-regulated in waste incinerating workers as compared with controls. Plasma proteins were analyzed by 2-dimentional electrophoresis with pH 3-10 NL IPG Dry strip. The protein expression profiles showed that 8 proteins were up- regulated and 1 protein, haptoglobin, was down- regulated in automobile emission inspectors and waste incineration workers. Serum paraoxonase/ arylesterase was found only in the plasma of waste incineration workers. The expression of genes and proteins involved in oxidative stress were up-regulated in both automobile emission inspectors and waste incineration workers. Several proteins, such as transthyrethin, sarcolectin and haptoglobin, that were highly up- or down-regulated, could serve as biological monitoring markers for future study.
Adult ; Aged ; Biological Markers/analysis ; DNA Fragmentation ; Environmental Monitoring/*methods ; Gene Expression Profiling ; Genetic Markers ; Genomics ; Humans ; *Incineration ; Middle Aged ; Naphthols/urine ; Occupational Exposure/analysis ; Oligonucleotide Array Sequence Analysis ; Polycyclic Hydrocarbons, Aromatic/analysis/*toxicity ; Proteomics ; Pyrenes/analysis ; Research Support, Non-U.S. Gov't ; Tetrachlorodibenzodioxin/analysis/*toxicity ; *Vehicle Emissions

OBJECTIVE: To investigate the expression of cytokines and growth factors in disc specimens obtained from small numbers of patients with herniated nucleus pulposus (HNP) and degenerated disc disease (DDD). METHOD: A total of ten human intervertebral disc samples consisted of five painful degenerative discs and five herniated intervertebal discs were obtained from surgery. MRI and Western blot analyses on these disc samples were performed to determine the levels of disc degeneration and the expression levels of cytokines and growth factors. RESULTS: The levels of IL-6 were significantly greater in the DDD patients than in the HNP patients, but no statistical differences were observed in the expression of IL-1beta, IL-8 and TNF-alpha between the HNP and DDD patients. In addition, the expression of TGF beta was significantly higher in the DDD patients than in the HNP patients. CONCLUSION: The higher levels of cytokine and growth factor expression in the DDD than in the HNP show why discogenic patients usually have more severe back pain than patients with herniated discs.
Back Pain ; Blotting, Western ; Cytokines ; Dichlorodiphenyldichloroethane ; Humans ; Intercellular Signaling Peptides and Proteins ; Interleukin-6 ; Interleukin-8 ; Intervertebral Disc ; Intervertebral Disc Degeneration ; Intervertebral Disc Displacement ; Tumor Necrosis Factor-alpha