Study On Biomarkers And Health Effects In Workers Exposed To Toluene Diisocyanate(TDI)

?Objective?1. To investigate the health damage effect of workers occupational exposed to toluene diisocyanate(TDI) and seek the effective markers.2. To explore the genetic damage effect of TDI exposed workers and the impact on exposure level and pulmonary function of metabolic gene polymorphisms.3. To study m RNA expression of epigenetic regulation and immunity related enzyme of TDI exposed workers, explore the pathogenesis of lung injury induced by TDI.?Methods?1. We adopted the cross-sectional study of epidemiology to analyze air sample of TDI exposed workplaces with fixed-point sampling method. The health data and biological samples of workers were collected to analyze the correlation between effect index and the exposure time and exposure levels of workers.2. Cytokinesis-block micronucleus cytome assay was chosen to analyze genetic damage effect of TDI exposed workers; the impact on exposure level and pulmonary function of metabolic gene polymorphisms was also analyzed.3. Real-time quantitative PCR method was used to detect the mRNA expression of epigenetic regulation and immunity related enzymes, and analyzed the correlation between various enzymes and the exposure time and exposure levels of TDI exposed workers.?Results?1. Compared with the control group, the exposed workers' lung ventilation function declined obviously. The level of FVC, FEV1.0 and FEV1.0/FVC of exposed workers was obviously lower than the control group, the difference was statistically significant(P<0.05); The number of PLT, MPV, LYM and NEUT cells of exposed workers was significantly higher than the control group(P<0.01);LDH, SDH and GSH activity in the peripheral blood serum of TDI exposed group were statistically lower than the control group(P<0.05).2. In the peripheral blood lymphocyte subsets, the differences of total T cells(CD3+),CD4+T cells and CD8+T cells, NK cells and B cells proportion between exposure group and the control group have no statistical significance(P > 0.05). IL- 6, MCP and MIP level in the peripheral blood serum of contact group workers is significantly higher than those in non-exposed controls(P<0.05).In peripheral blood serum, Ig G, Ig A and Ig M level between exposure group and the control group had no statistical difference(P > 0.05).3. Under the condition of same exposure, compared with the control group, lung function FEV1.0 / FVC levels of CYP1A1 gene wt/wt parting workers significantly reduced(P<0.05).Group under the condition of same exposure, FEV % FVC % of exposure CYP1A1wt/wt genotype is higher than that of wt/2a genotype, the difference was statistically significant(P<0.05). concentration of 2, 4-the TDA results of the contact group with CYP1A1wt/wt wt/2a genotype, NAT21 CC, TT and CT genotype, GSTP1 Ile/Ile, Ile/Val genotype,and GSTM1 and GSTT1 of wild missing genotype has a higher trend, differences have tatistically significant(P<0.05).Lung ventilation dysfunction rate differences of CYP1A1,GSTP1, GSTM1 and GSTT1 and NAT2 genotype in Contact group carriers had no statistical significance(P>0.05). In the inspection level 0.05, CYP1A1, GSTP1, GSTM1 and GSTT1 and NAT2 genotype had no statistical significance to determine whether there is a ventilation disorder(P>0.05).4. The relative expression of HDACm RNA, HATm RNA, Foxp3 m RNA, Me CP2 m RNA,DNMT1 m RNA have significant difference in contact and control groups,and expression level of contact group is higher than the control group(P<0.05).The expression level of HATm RNA and FVC, FEV1.0/FVC has significant correlation(P<0.05).HATm RNA,TSLPm RNA, ROR?t m RNA expression have a significant negative correlationwith 2, 4- the TDA concentration(r=0.382, P<0.01,r = 0.297, P=0.003; r=0.283, P=0.005), and the expression level of Foxp3 m RNA has a significant positive correlation with 2, 4-the TDA concentration(r=0.214, P=0.026).?Conclusion?1. Occupational exposure of TDI can induce the damage to lung ventilation function and cause inflammatory reaction to exposed workess; TDI also induce peripheral blood oxidative stress and the disorder of energy metabolism level of exposed workers.2. The changes of cytokines peripheral blood serum IL-6, MCP, MIP level may caused by TDI occupational exposure;3. CYP1A1, GSTM1 and GSTT1 gene polymorphisms can affect the level of workers lung ventilation function,CYP1A1, NAT2, GSTT1, GSTP1 gene polymorphism may affect the metabolism of TDI.4. The value of Foxp3 gene m RNA have a rising trend, and it prompt Treg cells involved in lung injury cause by TDI occupational exposure, the differentiation of the cells, cytokines release of epigenetic regulation maybe its possible pathogenesis.