OBJECTIVETo compare PM2.5 pollation level between the city of coal-fuel pollution (Taiyuan) and the city of pollution mixed with coal fuels and vehicle exhausts (Beijing), to analyze the concentration of B[a]p and Pb in the pollutants, and to study the DNA damage by PM2.5.

METHODSAir fine particles (PM2.5) were collected in Beijing and Taiyuan by means of the filter membrane method, the concentration of B[a]p and Pb were analyzed by high performance liquid chromatography and atomic absorption spectroscopy respectveily, and the damage of DNA by PM2.5 was detected by single cell gel-electrophoresis (SCGE) using the human lung epithelial cells (A549) as target cells.

RESULTSThe concentration of PM2.5 in the winter of Beijing was 0.028-0.436 mg/m(3), and that in Taiyuan was 0.132-0.681 mg/m(3). The concentration of B[a]p was 0.104 and 0.156 microg/mg on PM2.5 of Beijing and Taiyuan, respectively, whereas the concentration of Pb was 1.094 and 1.137 microg/mg on PM2.5 of Beijing and Taiyuan, respectively. Exposure to PM2.5 at the concentrations of 5, 50, and 200 microg/mL for 12 h and 24 h caused DNA damage of the human alveolar epithelium, and the ratios of the tailing and length of the tail were all significantly different from those of the negative control group (P < 0.05), and indicated a dose-response relationship.

CONCLUSIONPM2.5 has certain genetic toxicity.

Air Pollutants ; analysis ; toxicity ; Animals ; Benzo(a)pyrene ; analysis ; toxicity ; China ; DNA Damage ; drug effects ; Dose-Response Relationship, Drug ; Drug-Related Side Effects and Adverse Reactions ; Environmental Monitoring ; methods ; Humans ; Lead ; analysis ; metabolism ; toxicity ; Particle Size ; Pulmonary Alveoli ; drug effects ; metabolism ; Seasons

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants present in air and food. Among PAHs, benzo(a)pyrene(BaP), phenanthrene (PH) and pyrene (PY) are considered to be important for their toxicity or abundance. To investigate the changes of biomarkers after PAH exposure, rats were treated with BaP (150 microgram/kg) alone or with PH (4,300 microgram/kg) and PY (2,700 microgram/kg) (BPP group) by oral gavage once per day for 30 days. 7-ethoxyresorufin-O-deethylase activity in liver microsomal fraction was increased in only BaP groups. The highest concentration (34.5 ng/g) of BaP, was found in muscle of rats treated with BaP alone at 20 days of treatment; it was 23.6 ng/g in BPP treated rats at 30 days of treatment. The highest PH concentration was 47.1 ng/g in muscle and 118.8 ng/g in fat, and for PY it was 29.7 ng/g in muscle and 219.9 ng/g in fat, in BPP groups. In urine, 114-161 ng/ml 3-OH-PH was found, while PH was 41-69 ng/ml during treatment. 201-263 ng/ml 1-OH-PY was found, while PH was 9-17 ng/ml in urine. The level of PY, PH and their metabolites in urine was rapidly decreased after withdrawal of treatment. This study suggest that 1-OH-PY in urine is a sensitive biomarker for PAHs; it was the most highly detected marker among the three PAHs and their metabolites evaluated during the exposure period and for 14 days after withdrawal.
Adipose Tissue/chemistry/drug effects ; Animals ; Benzo(a)pyrene/analysis/metabolism/*toxicity ; Biological Markers/metabolism/urine ; Blood Chemical Analysis ; Body Weight/drug effects ; Cytochrome P-450 CYP1A1/metabolism ; Environmental Pollutants/blood/metabolism/*toxicity/urine ; Female ; Liver/drug effects/enzymology ; Lymphocytes/drug effects/metabolism ; Muscle, Skeletal/drug effects/metabolism ; Organ Size/drug effects ; Phenanthrenes/blood/metabolism/*toxicity/urine ; Pyrenes/analysis/metabolism/*toxicity ; Rats ; Rats, Sprague-Dawley ; Time Factors

OBJECTIVETo investigate the effects of mitogen activated protein kinase (MAPK) signal transduction pathways on heat shock protein 70 (HSP70) gene expression in endothelial cells exposed to benzo(a)pryene (BaP).

METHODSPorcine aortic endothelial cells were pre-treated or by PD98059 (10 micro mol/L) or SB203580 (20 micro mol/L) for 1 hour, then treated with different concentrations of BaP (0, 0.1, 0.5, 1.0, 5.0 and 10.0 micro mol/L) for 24 hours respectively;Expression levels of three phosphorylated MAPKs [extracellular signal regulated protein kinase (ERK), c-Jun amino-terminal kinase (JNK), and p38] and HSP70 were determined by Western-blot.

RESULTSThe three phosphorylated MAPKs expressional levels especially p-ERK1 had different extents of changes with dose-response relationship under BaP exposure. BaP inhibited the expression of HSP70, which significantly decreased in medium and high dose group (>or= 1.0 micro mol/L) but did not decrease in control group (P < 0.05). Although the inhibitor of ERK (PD98059) could partly weaken the inhibited effects of BaP on HSP70 expression, HSP70 expression levels of endothelial cells pre-treated with PD98059 were still significantly lower than that of control cells (P < 0.05).

CONCLUSIONERK1 pathway might play some roles in HSP70 gene expression in endothelial cells exposed to BaP, and other unknown signal pathways might also have some effects on this process.

Animals ; Benzo(a)pyrene ; toxicity ; Blotting, Western ; Dose-Response Relationship, Drug ; Endothelial Cells ; drug effects ; metabolism ; Enzyme Inhibitors ; pharmacology ; Flavonoids ; pharmacology ; HSP70 Heat-Shock Proteins ; analysis ; Imidazoles ; pharmacology ; JNK Mitogen-Activated Protein Kinases ; MAP Kinase Kinase 4 ; Mitogen-Activated Protein Kinase Kinases ; analysis ; Mitogen-Activated Protein Kinases ; analysis ; antagonists & inhibitors ; Pyridines ; pharmacology ; Signal Transduction ; physiology ; Swine ; p38 Mitogen-Activated Protein Kinases

BACKGROUNDThe present study was designed to examine and analyze the global gene expression changes during the tumorigenesis of a human immortalized oral epithelial cell line, and search for the possible genes that may play a role in the carcinogenesis of oral cancer associated with benzo (a) pyrene.

METHODSThe human immortalized oral epithelial cells, which have been established through transfection of E6/E7 genes of human papillomavirus type 16 and proved to be non-tumorigenic in nude mice, were treated with benzo (a) pyrene. Tumorigenicity of the treated cells were examined through nude mice subcutaneous injection. The global gene expression profiles of immortalized cells and the tumorigenic cells were acquired through hybridization of a microarray of Affymetrix U133 plus 2.0. The data were analyzed using Spring 7.0 software and treated statistically using one-way analysis of variance (ANOVA). The differentially expressed genes were classified using a Venn diagram and annotated with gene ontology. Several highlighted genes were validated in cells using a real-time polymerase chain reaction.

RESULTSThere were 883 differentially expressed genes during the tumorigenesis and most of them changed expression in the early stage of tumorigenesis. These genes mainly involved in macromolecule metabolism and signal transduction, possessed the molecular function of transition metal ion binding, nucleotide binding and kinase activity; their protein products were mainly integral to membranes or localized in the nucleus and cytoskeleton. The expression patterns of IGFBP3, S100A8, MAP2K, KRT6B, GDF15, MET were validated in cells using a real-time polymerase chain reaction; the expression of IGFBP3 was further validated in clinical oral cancer specimens.

CONCLUSIONSThis study provides the global transcription profiling associated with the tumorigenesis of oral epithelial cells exposed to benzo (a) pyrene; IGFBP3 may play a potential role in the initiation of oral cancer related to benzo (a) pyrene exposure.

Benzo(a)pyrene ; toxicity ; Cell Transformation, Neoplastic ; Cells, Cultured ; Connexin 43 ; genetics ; Gene Expression Profiling ; Growth Differentiation Factor 15 ; genetics ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Proteins ; genetics ; Mouth Neoplasms ; chemically induced ; metabolism ; Oligonucleotide Array Sequence Analysis ; Reverse Transcriptase Polymerase Chain Reaction