氯乙烯作业工人遗传损伤与免疫功能的关系

发布时间：2018-04-12 11:29

本文选题：氯乙烯 + 遗传损伤　；参考：《复旦大学》2013年硕士论文

【摘要】：氯乙烯(vinyl chloride, VC)是一种重要的化工原料,约95%用于合成聚氯乙烯(polyvinyl chloride, PVC),是确定的人类致癌物。目前我国是世界上最大的PVC消费国和生产国,众多VC接触工人的健康问题值得关注。 1974年首次报道高浓度VC接触工人发生肝血管肉瘤病例,1987年IARC将其划分为确定的人类致癌物,可导致多系统、多器官肿瘤的发生,其主要靶器官是肝脏。随着对VC毒性认识的加深,各国都在严格控制工作场所空气中VC的浓度。目前西方发达国家VC的职业接触限值多为1ppm (2.79mg/m3),我国工业场所VC时间加权平均浓度(PC-TWA)修订为10mg/m3(GBZ2.1-2007),短时间接触容许浓度为(PC-STEL)为20mg/m3,仍是西方发达国家职业卫生标准的数倍。有必要探讨我国现行职业卫生标准条件下,VC对作业工人的健康危害。本研究根据历年车间空气中VC浓度监测结果、性别、工龄计算累积接触剂量,按累积接触剂量将接触组分为低、中、高三个剂量组(累积接触剂量：353.58--893.07mg为低剂量组；893.07--30071.77mg为中等剂量组；30071.77--179808.03mg为高剂量组)。探讨VC作业工人遗传损伤、免疫功能状况,研究分析VC作业工人遗传损伤、VC接触对作业工人免疫功能影响的影响因素,探索VC作业工人遗传损伤及免疫功能之间的关联。为探寻VC接触工人的效应标志和最终保护VC接触人群的健康,提供科学依据。选择2012年参加体检的上海某化工厂VC作业工龄超过一年的工人95人(男73人,女22人)为接触组,选择同期体检的该公司行政和后勤管理人员32人(男18人,女14人)(工作岗位远离厂区,无VC及其他毒物职业接触史)作为对照组。采用胞质分裂阻滞微核试验(CB-MN, cytokinesis-block micronucleus assay)对研究对象进行染色体损伤检测,结果显示VC接触组外周血淋巴细胞微核细胞率(简称微核率)为(3.19±1.76)‰,显著高于对照组(1.91±1.36)%o, FR=1.67(95%CI1.27-2.20, P0.001),且低、中、高接触剂量组的微核率与累积接触剂量间存在剂量-反应关系,提示微核率可以作为评价低浓度VC接触的效应指标。多因素分析发现VC接触、吸烟情况、年龄对染色体损伤有影响。以低龄组(≤5岁)为参比,大龄组(35岁)FR值为1.49(95%CI1.17-1.89),大年龄组(35岁)染色体损伤风险高,因此应加强对大年龄组(35岁)工人的健康监护。与对照组相比,VC接触组FR值为1.69,95%CI为(1.29-2.22),VC接触组染色体损伤风险高。采用ELISA法对上述研究对象的细胞免疫功能指标(IL-6、TNF-a, IFN-r)、体液免疫功能指标(IgA、IgG、IgM)进行检测、分析,结果显示VC接触组和对照组细胞免疫功能指标(IL-6、TNF-α、IFN-γ)检测结果差异无统计学意义(p0.05),体液免疫功能指标中等剂量接触组IgG、IgM表达量(71.6±10.78、181.38±80.01)高于对照组(12.3±11.47、120.57±50.33),差异有统计学意义(p0.05),而IgA结果差异无统计学差异(p0.05)。多因素分析发现VC接触、饮酒对免疫功能有影响。结果显示中接触剂量组IL-6, IgG表达量显著高于对照组(p0.05,p0.001)。中、高剂量接触组IgM表达量显著高于对照组(p0.001,p0.001),饮酒组IgM表达量显著高于非饮酒组(p＜0.05)。IL-6、IgG、IgM在VC作业工人健康监护中可能具有一定意义。采用秩相关,分析微核率与IL-6、TNF-α、IFN-γ、IgA、IgG、IgM表达水平的相关性。结果显示,低剂量接触组工人微核率与IFN-r表达水平相关系数为-0.40(p0.05),中剂量接触组微核率与IgA表达水平相关系数为0.35(p0.05),其余剂量接触组微核率与免疫指标表达水平相关性无统计学意义(p0.05)。选择发生染色体损伤(微核率4‰)且免疫指标表达异常的研究对象,分析染色体损伤与免疫功能的相关性。结果显示,低剂量接触组染色体损伤与TNF-a表达异常相关系数为1.00(p0.05),高剂量接触组染色体损伤与IFN-r表达异常相关系数为0.79(p0.05),低剂量接触组染色体损伤与IgM表达异常相关系数为1.00(p0.05)。染色体损伤与与免疫功能相关性分析显示,发生染色体损伤与免疫指标表达异常相关性较高,提示TNF-α、IFN-γ、IgM表达异常与遗传损伤发生可能有一定关联。综上所述,在低于我国目前职业卫生标准的接触浓度情况下,VC接触工人的微核率较对照组显著增加,微核率可以作为VC接触工人遗传损伤的敏感指标。在我国现行职业卫生标准下,VC接触可对作业工人免疫功能产生影响,IgG、IgM作为评价低浓度VC接触的效应指标还需进一步研究论证。遗传损伤与免疫功能相关性分析结果提示,免疫指标表达异常与遗传损伤发生可能有一定关联。
[Abstract]:Vinyl chloride (vinyl chloride VC) is an important chemical raw materials, about 95% for the synthesis of PVC (polyvinyl, chloride, PVC) is a human carcinogen. At present, China is the world's largest consumer and producer of PVC, many VC workers exposed to health problems worthy of attention.
For the first time in 1974 reported a high concentration of VC in workers exposed to hepatic angiosarcoma cases, 1987 IARC will be divided into confirmed human carcinogen, can cause multi system, multi organ carcinogenesis, the target organ is the liver. With the understanding of the toxicity of VC deeply, all the countries in the strict control of the concentration of VC in the air of workplaces. The occupation contact of western developed countries VC limit value is 1ppm (2.79mg/m3), VC time weighted China industrial sites average concentration (PC-TWA) of 10mg/m3 (GBZ2.1-2007), revised STEL for (PC-STEL) 20mg/m3, standard of occupation health in western developed countries is still several times. It is necessary to study China's current standard of occupation health conditions, health hazards of workers exposed to VC.
According to the calendar year in the air of workplace VC concentration monitoring results, gender, length of service calculated cumulative exposure dose, according to the cumulative exposure dose will contact were divided into low, medium and high dose groups (cumulative exposure dose: 353.58--893.07mg low dose group middle dose group; 893.07--30071.77mg; 30071.77--179808.03mg for high dose group). To investigate the VC operation the genetic damage of workers, immune function, research and analysis of VC workers genetic damage, the influence factors of the VC contact effect on the immune function of workers, to explore the association between genetic damage and immune function of workers in VC. To explore the VC contact effect markers of workers and ultimately protect the VC contact the health of the population, to provide a scientific basis.
A chemical plant in Shanghai VC years of working in 2012 to participate in the examination of more than a year of 95 workers (male 73, female 22) as the contact group, select the same physical examination the company administration and logistics management staff of 32 people (male 18, female 14) (jobs away from the factory, no VC and he occupation poison contact history) as the control group. The cytokinesis block micronucleus test (CB-MN cytokinesis-block, micronucleus assay) of chromosome damage detection on the object of study, results showed that the lymphocyte micronucleus rate of peripheral blood VC exposure group (referred to as the micronucleus rate) for (3.19 + 1.76)%, significantly higher than the control group (1.91 + 1.36)%o FR=1.67, (95%CI1.27-2.20, P0.001), and low, high dose group, contact the micronucleus rate and the dose-response relationship between cumulative exposure dose, suggesting that the micronucleus rate can be used as index to evaluate the effect of low concentration of VC contact.
Multivariate analysis showed that VC exposure, smoking, age effects on chromosomal damage. In the younger group (< 5 years) as a reference, the older group (35 years old) FR 1.49 (95%CI1.17-1.89), age group (35 years old) the risk of chromosome damage is high, so we should strengthen the large age group (35 old) health care workers. Compared with the control group, VC group, FR contact = 1.69,95%CI (1.29-2.22), VC exposure group chromosomal damage in high risk.
Using the ELISA method to the study of cell immune function index (IL-6, TNF-a, IFN-r), humoral immune function indexes (IgA, IgG, IgM) were detected. The analysis results showed that VC exposure group and control group cell immune function indexes (IL-6, TNF- alpha, gamma IFN-) there was no significant difference (test results P0.05), humoral immune function indexes of moderate dose exposure group IgG, the expression of IgM (71.6 + 10.78181.38 + 80.01) higher than that of the control group (12.3 + 11.47120.57 + 50.33), the difference was statistically significant (P0.05), but there was no difference between the results of IgA (P0.05).
Multivariate analysis showed that VC contact, drinking has effect on immune function. The results showed that in the exposed dose group IL-6, IgG expression was significantly higher than that of the control group (P0.05, p0.001). In high dose exposure group IgM expression was significantly higher than that of the control group (p0.001, p0.001), drinking group the expression of IgM was significantly higher than that of the non drinking group (P < 0.05).IL-6, IgG, IgM may have a role in health care workers in VC.
The rank correlation analysis, the micronucleus rate and IL-6, TNF- alpha, IFN- gamma, IgA, IgG, the expression level of IgM gene. The results showed that the group of workers micronucleus rate and the expression level of IFN-r correlation coefficient for -0.40 exposure to low dose (P0.05) group, micronucleus rate and the expression level of IgA correlation coefficient was 0.35 in dose exposure (P0.05 the rest of the contact group), dose of micronucleus rate and immune index expression correlation was not statistically significant (P0.05). Incidence of chromosomal damage (micronucleus rate of 4 per thousand) and immune index of abnormal expression of object, analysis of the correlation between chromosomal damage and immune function. The results showed that exposure to low dose group chromosomal damage and abnormal expression of TNF-a correlation coefficient 1 (P0.05), high dose exposure group chromosomal damage and abnormal expression of IFN-r correlation coefficient is 0.79 (P0.05), low dose exposure group chromosomal damage and abnormal expression of IgM correlation coefficient is 1 (P0.05). Chromosomal damage Correlation analysis with immune function showed that there was a high correlation between chromosomal damage and abnormal expression of immune indicators, suggesting that the abnormal expression of TNF-, IFN- and IgM may be associated with genetic damage.
In conclusion, the micronucleus rate of workers exposed to VC is significantly higher than that of the control group, and the micronucleus rate can be used as a sensitive indicator for genetic damage of workers exposed to VC.
In the current occupation health standard of our country, VC exposure can affect the immune function of workers exposed to IgG, IgM as evaluation index of effect of low concentration VC exposure also need to be further studied. The genetic damage of immune function and the correlation analysis showed that the abnormal expression of immune index and genetic damage may be related.

【学位授予单位】：复旦大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R135

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