| ObjectiveCoke oven emissions (COE) is made from bituminous coal in coke oven chamber through retort process, which is lack of oxygen and in high temperature, and diffused to the outside in other process of production. COE is compound of gas, steam and smoke, including many carcinogens or promoting carcinogen, and widely exists in aluminium, steel, graphite, electrical, construction and other industries. COE is not only harmful to the environment, especially the air, also to the health of occupational exposed population. Chronic long-term exposured to COE, the damage of respiratory system, digestive system, as well as conjunctivitis and other disease could occur in workers. Cancer is the major problem of COE exposure, the International Agency for Research on Cancer (IARC) has identified COE as the class 1 carcinogen, China has put lung cancer caused by COE in occupational tumors. In the guardianship of coke oven workers’health, the damage effect in blood system and mechanism studies reported less besides the carcinogenic effects, this occupational health problem is to be solved.Exogenous chemicals are absorbed into the blood stream firstly, achieve a high concentration, and the metabolic process also rely on blood, so all kinds of blood cells in peripheral blood are vulnerable. The outcomes of the blood toxicity mainly have abnormal blood cells generation, abnormal hemoglobin (HGB) and hemorrhagic diseases, etc. We adopted cross-sectional epidemiological design, chose coke oven workers as the target population, detected the COE concertration of working environment and in coke oven workers, examined the blood routine, to evaluat the relationship between different COE exposure levels and blood system damage. On this basis, we built the cell model to explore the toxicity of human blood cells caused by COE. We examined the cell toxicity, oxidative damage, genetic material damage and the protein expression of the nuclear factor-KB (NF-κB) pathway, to looking for the key pathways, clarify the biological mechanisms preliminarily, provide important basis to further perfect the health damage effect assessment of COE and health care scheme of coke oven workers.Methods1. The epidemiological analysis of hematotoxicity caused by COEWe chose 263 coke workers in-service in a coking plant of Shandong Province as the exposure group,133 workers of an oxygen installation beyond 3km distance from the coking plant were chosen as the control group, which had no clear kidney disease nearly one year. The uniform questionnaire survey, general physical examination, routine blood test and other items were processed. The questionnaire survey mainly included personal general condition, working experience, smoking, drinking, medical history and present illness. The urine after work was collected 30-50 ml. The concentration of 1-hydroxypyrene (1-OHP) in urine was detected by high performance liquid chromatography (HPLC), the concentration of 8-hydroxy-2’-deoxyguanosine (8-OHdG) in urine was detected by the ultra-high performance liquid chromatography (UPLC)-mass spectrometry (MS). In addition, the creatinine concentration in urine was detected by UPLC to rectify the concentration of 1-OHP and 8-OHdG individual differences.2. The mechanism exploration of hematotoxicity caused by COEWe chose human acute promyelocytic leukemia cells (HL-60) as experiment cells, COE organic extracts as infected material, the content of fetal bovine serum (FBS) in medium was 5%. Dissolved the extract stock solution into medium to the final concentration of 2.5,5,10 and 20μg/ml,1% DMSO was the control group.The exposed time were 24h and 4d. We chose the CCK-8, lactate dehydrogenase (LDH) and propidium iodide (PI)/fluorescein isothiocyanate (FITC) flow cytometry methods to detect the toxic effects of cells, dichlorofluorescein diacetate (DCFH-DA) fluorescent probe to detect ROS levels intracellular, nitro bt dye to detect ROS levels extracellular, single cell gel electrophoresis (SCGE) to detect the DNA damage of cells, Western-blot to detect the protein expression of NF-κB pathway.Results1. The epidemiological analysis of hematotoxicity caused by COEThe concentration of COE in working environment of the coking plant was more than five times of the control plant, the correlation of COE concentration in working environment and working position was significant (P<0.05). Compared with control group, the concentration of 1-OHP in urine of exposed group workers were significantly higher (P<0.05). Remove the influence of gender, age, body mass index (BMI), smoking and drinking, the correlation between 1-OHP concentration in urine with exposed COE or not was significant (P<0.05), which prompted that the concentration of 1-OHP in urine could be used as COE occupational exposure inside level of coke workers.The concentration of 8-OHdG in urine of exposed group workers was 51.3% higher than the control group (P<0.05), and the linear positive correlation between it and 1-OHP concentration in urine was significant (P<0.05), which prompted that COE occupational exposure could produce certain DNA oxidative damage, so the risk of cancer was higher.In the blood routine test, the white blood cell count (WBC) level of exposed group workers were lower, but the difference was not significant (P>0.05). Among the exposed group workers, the WBC declined with 8-OHdG level in urine increased, which had a critical significant difference (P= 0.055).2. The mechanism exploration of hematotoxicity caused by COEAll of three cytotoxicity experimental results (CCK 8, LDH, PI/FITC) had shown that COE had damaging effects for human blood cells. Compared with control group, the cell survival rate declined (P<0.05), the ROS levels of cells released increased (P<0.05), the DNA damage of cells increased (P<0.05), and the damage degree of 4d experiments was higher than 24h, the protein expression of NF-κB pathway increased (P<0.05) with the COE dose increased. In 24h experiments, compared with the COE 2.5μg/ml dose group, the protein expressions of IκBα and NF-κB p65 decreased with the COE dose increased (P<0.05), while the protein expressions of phosphorylation IκBα and phosphorylation NF-κB p65 increased (P<0.05). In 4d experiments, the protein expression of two groups were both increased (P<0.05), there was a good dose effect relationship.Conclusion1. The COE could lead the number of blood cells changed to the occupational exposure population, which may be associated with DNA oxidative damage.2. The COE could cause a certain degree of oxidative and genetic material damage in the HL-60 cell in vitro, and the damage could be aggravating with the increase of COE dose.3. The damage of white blood cells caused by COE might be related to the activation of the NF-κB pathway. |
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