苯及其代谢物对血液毒性的研究
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摘要
目的
通过现场调查和体外实验,研究苯及其代谢物对血液系统的损伤作用和部分机理,探讨苯作业工人内暴露水平与血液系统外周血部分细胞指标和生化指标相关关系,以丰富苯对血液系统的毒性作用机理的认识。
方法
一、第一部分选择某制鞋厂57名接苯工人和26名非接苯工人为研究对象,采用高效液相色谱法(HPLC)测定研究对象班末尿苯巯基尿酸含量(肌酐校正),并对其外周血细胞数量、淋巴细胞结构、血中细胞色素氧化酶和谷胱甘肽硫转移酶活性的变化进行观察,分析两者间相关关系。
二、第二部分通过体外染毒实验研究,运用微核、染色体G-分带和彗星检测方法,观察不同浓度苯的代谢产物氢醌、1,2,4-苯三酚单独及联合作用对人外周血淋巴细胞染色体结构的影响和DNA损伤的情况。
结果
一、第一部分与对照组比较,暴露组工人血象各指标有下降趋势、血清CYP2E1活力有升高趋势,但经统计分析后显示上述指标各组间差异无显著性。血清GST活力则明显高于对照组。高、低暴露组和对照组淋巴细胞微核(MN)率分别为9.00‰、4.00‰、2.00‰,差异呈显著性,工人外周血淋巴细胞微核率与其班后尿SPMA浓度存在明显的剂量-反应关系(r=0.678,P<0.001),且工人工龄与其外周血淋巴细胞微核率之间也存在着较好的剂量-反应关系(r=0.515,P=0.002)。
二、第二部分氢醌、1,2,4-苯三酚单独染毒与联合染毒时,淋巴细胞微核细胞(MN)率,淋巴细胞染色体畸变(CA),淋巴细胞DNA损伤与染毒剂量存在明显的剂量—反应关系,且联合染毒与两种代谢物单独染毒相比较,呈显著性增高,表明这两种代谢物之间存在协同作用。
结论
1在接苯作业情况下,作业环境空气苯浓度与工人尿中SPMA浓度、工人尿SPMA浓度与淋巴细胞微核率、工人工龄与淋巴细胞微核率间均有差异;血清GST活力变化对早期诊断苯中毒有一定的指导意义。
2氢醌、1,2,4-苯三酚可致人外周淋巴细胞染色体和DNA损伤,且呈剂量-反应关系,同时两者间呈协同作用。
Purpose
Through on-site investigation and in vitro study of benzene and its metabolites on the blood system and the role of part of the mechanism of injury, and explore the benzene exposure levels in workers exposed to blood and peripheral blood system cells, some of the indicators and related biochemical indicators in order to enrich the blood of benzene The toxic mechanism of the system.
Methods
1、First part Select a shoe factory next 57 benzene workers and 26 non-workers access to the study, using high performance liquid chromatography (HPLC) determination study class at the end of SH-urinary uric acid content (creatinine correction), and The number of peripheral blood cells, lymphocytes structure of the blood in the cytochrome oxidase and glutathione S-transferase activity changes observed analysis of the relationship between the two.
2、Second part Through exposure in vitro experiments, using micronucleus, chromosome G-banding and comet detection methods to observe the different concentrations of benzene metabolite of hydroquinone, 1, 2, 4 - phloroglucinol separate and combined effects of human peripheral blood lymphocytes Chromosome structure and DNA damage.
Results
1、First part
Compared with the control group, the exposed group’s blood indicators have a declining trend, and serum CYP450 activity has a increasing trend, but the statistical analysis shows that the indicators’difference are not significant. Each group of the average serum GST activity: high-exposure group is 20.73μ/ml, low-exposure group is 22.62U/ml, the control group is 17.78μ/ml, among the three groups have a significant difference (p=0.003), two-two comparison show that high-exposure and control group、low-exposure and control group are significantly different (p=0.003), while the two exposure group reveal no statistically significant difference (p=0.975). Micronucleus rate of lymphocyte in the peripheral blood of high-and low-exposure and control group are respectively 9.00‰、4.00‰、2.00‰, the analysis found that among the three groups have statistical significance (p<0.01), moreover the micronucleus rate and the concentration of urine S-PMA have a clear dose-response relationship (r=0.678, p<0.001). Between the two exposure group, the concentration of air benzene and urine S-PMA are not significantly different, but they have a remarkable dose-response relationship (r=0.95, p<0.001), the length of service and micronucleus rate also exist good dose-response relationship (r=0.515, p=0.002).
2、Second part
Hydroquinone, 1,2,4-Phloroglucinol ecposure and a separate joint exposure, micro-lymphocyte cells (MN) rate of lymphocyte chromosome aberrations (CA), lymphocyte DNA damage and there is an obvious dose of Dose-response relationship, and the two mebabolites of exposure and exposure alone, compared to a significant increase of these two metabolites that exists between the synergies.
Conclusion
1、In the benzene-exposure operating circumstances, the concentration of air benzene and urine S-PMA、urine S-PMA concentration and micronucleus rate、the length of service and micronucleus rate, all have the good dose-response relationship; the changes of serum GST activity is a certain significance to early diagnosis of benzene poisoning.
2、It suggests that BT and HQ could induce chromosome damage on human peripheral lymphocyte and have synergetic effect.Comet assay is a test DNA damage in peripheral blood lymphocytes sensitive indicators.
通过现场调查和体外实验,研究苯及其代谢物对血液系统的损伤作用和部分机理,探讨苯作业工人内暴露水平与血液系统外周血部分细胞指标和生化指标相关关系,以丰富苯对血液系统的毒性作用机理的认识。
方法
一、第一部分选择某制鞋厂57名接苯工人和26名非接苯工人为研究对象,采用高效液相色谱法(HPLC)测定研究对象班末尿苯巯基尿酸含量(肌酐校正),并对其外周血细胞数量、淋巴细胞结构、血中细胞色素氧化酶和谷胱甘肽硫转移酶活性的变化进行观察,分析两者间相关关系。
二、第二部分通过体外染毒实验研究,运用微核、染色体G-分带和彗星检测方法,观察不同浓度苯的代谢产物氢醌、1,2,4-苯三酚单独及联合作用对人外周血淋巴细胞染色体结构的影响和DNA损伤的情况。
结果
一、第一部分与对照组比较,暴露组工人血象各指标有下降趋势、血清CYP2E1活力有升高趋势,但经统计分析后显示上述指标各组间差异无显著性。血清GST活力则明显高于对照组。高、低暴露组和对照组淋巴细胞微核(MN)率分别为9.00‰、4.00‰、2.00‰,差异呈显著性,工人外周血淋巴细胞微核率与其班后尿SPMA浓度存在明显的剂量-反应关系(r=0.678,P<0.001),且工人工龄与其外周血淋巴细胞微核率之间也存在着较好的剂量-反应关系(r=0.515,P=0.002)。
二、第二部分氢醌、1,2,4-苯三酚单独染毒与联合染毒时,淋巴细胞微核细胞(MN)率,淋巴细胞染色体畸变(CA),淋巴细胞DNA损伤与染毒剂量存在明显的剂量—反应关系,且联合染毒与两种代谢物单独染毒相比较,呈显著性增高,表明这两种代谢物之间存在协同作用。
结论
1在接苯作业情况下,作业环境空气苯浓度与工人尿中SPMA浓度、工人尿SPMA浓度与淋巴细胞微核率、工人工龄与淋巴细胞微核率间均有差异;血清GST活力变化对早期诊断苯中毒有一定的指导意义。
2氢醌、1,2,4-苯三酚可致人外周淋巴细胞染色体和DNA损伤,且呈剂量-反应关系,同时两者间呈协同作用。
Purpose
Through on-site investigation and in vitro study of benzene and its metabolites on the blood system and the role of part of the mechanism of injury, and explore the benzene exposure levels in workers exposed to blood and peripheral blood system cells, some of the indicators and related biochemical indicators in order to enrich the blood of benzene The toxic mechanism of the system.
Methods
1、First part Select a shoe factory next 57 benzene workers and 26 non-workers access to the study, using high performance liquid chromatography (HPLC) determination study class at the end of SH-urinary uric acid content (creatinine correction), and The number of peripheral blood cells, lymphocytes structure of the blood in the cytochrome oxidase and glutathione S-transferase activity changes observed analysis of the relationship between the two.
2、Second part Through exposure in vitro experiments, using micronucleus, chromosome G-banding and comet detection methods to observe the different concentrations of benzene metabolite of hydroquinone, 1, 2, 4 - phloroglucinol separate and combined effects of human peripheral blood lymphocytes Chromosome structure and DNA damage.
Results
1、First part
Compared with the control group, the exposed group’s blood indicators have a declining trend, and serum CYP450 activity has a increasing trend, but the statistical analysis shows that the indicators’difference are not significant. Each group of the average serum GST activity: high-exposure group is 20.73μ/ml, low-exposure group is 22.62U/ml, the control group is 17.78μ/ml, among the three groups have a significant difference (p=0.003), two-two comparison show that high-exposure and control group、low-exposure and control group are significantly different (p=0.003), while the two exposure group reveal no statistically significant difference (p=0.975). Micronucleus rate of lymphocyte in the peripheral blood of high-and low-exposure and control group are respectively 9.00‰、4.00‰、2.00‰, the analysis found that among the three groups have statistical significance (p<0.01), moreover the micronucleus rate and the concentration of urine S-PMA have a clear dose-response relationship (r=0.678, p<0.001). Between the two exposure group, the concentration of air benzene and urine S-PMA are not significantly different, but they have a remarkable dose-response relationship (r=0.95, p<0.001), the length of service and micronucleus rate also exist good dose-response relationship (r=0.515, p=0.002).
2、Second part
Hydroquinone, 1,2,4-Phloroglucinol ecposure and a separate joint exposure, micro-lymphocyte cells (MN) rate of lymphocyte chromosome aberrations (CA), lymphocyte DNA damage and there is an obvious dose of Dose-response relationship, and the two mebabolites of exposure and exposure alone, compared to a significant increase of these two metabolites that exists between the synergies.
Conclusion
1、In the benzene-exposure operating circumstances, the concentration of air benzene and urine S-PMA、urine S-PMA concentration and micronucleus rate、the length of service and micronucleus rate, all have the good dose-response relationship; the changes of serum GST activity is a certain significance to early diagnosis of benzene poisoning.
2、It suggests that BT and HQ could induce chromosome damage on human peripheral lymphocyte and have synergetic effect.Comet assay is a test DNA damage in peripheral blood lymphocytes sensitive indicators.
引文
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[6]张巧,陈小玉等.长期低剂量苯接触对油漆工T淋巴细胞亚群的影响.河南医科大学学报.2000 ,36(6):530-532.
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[13] LiQ ,Kasten-Jolly J ,Yen Y ,et al. Reversal of hydroquinone-mediated suppression of T cell proliferation by transfection of the M2 subunit of ribonucleotide reductase. Toxicol Appl Pharmacol,1998;150:154-157.
[14]李华,刘欧.低浓度苯对大鼠T细胞亚群的影响.中国工业医学杂志,2002,15(6):356-357.
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[16]陈嘉榆,刘薇薇,等.苯接触工人外周血T细胞受体TCRV-β亚家族基因多肽性分析.中国工业医学杂志,2003,16:148-151.
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[20]高丽媛.苯作业工人免疫指标测定分析[J].河南预防医学杂志,1994,5(4):198-200.
[21] Bogadi Sare A ,Zavalic M,Trosic I ,et al . Study of some immunological parameters in workers occupationally exposed to benzene[J] . Int Arch Occup Environ Health ,2000 , 73(6) :397-400.
[22]扬建勋,陈应学,刘居峰.低浓度混苯作业工人免疫功能影响的探讨[J ].河南医学研究,1996,5(1):18-19
[23]刘希英,段建华,黄振学,等.苯对人红细胞免疫毒性研究[J].化工劳动保护(工业卫生与职业病分册),1996,17(2):52-53.
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[25] Wolman SR. Cytologic and cytogenetic effects of benzene[J].J Toxicol Environ Health Suppl,1977,2:63-68.
[26] Hayes RB,Snognian Y, Dosemeci M, linet M. Benzene and lymphohematopoietic malignancies in humans [J].Am J and Med,2001,40(2):117-26.
[27] Shen Y , Shen HM, Shi CY,Ong CN.Benzene metabolites enhance reactive oxygen species generation in HL60 human leukemia cells[J].Hum Exp Toxicol,1996,15(5):422-427.
[28]武南,黄芳.苯作业对工人外周血液的毒性作用.预防医学情报杂志2005, 21( 3 ):271-272.
[29]朱志良,等. 1,2,4-苯三酚与氢醌对人外周血淋巴细胞染色体的损伤研究.实用预防医学.2005,12(1):6-8.
[30] Lam TH , Zhu CQ , Jiang CQ , et al . Lymphocyte DNA damage in elevator manufacturing workers in Guangzhou , China [J ] . Mutat Res , 2002 , 515(122) : 1472157.
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[32]张美荣,赵华硕,等.苯致小鼠淋巴细胞DNA、RNA损伤作用.中国公共卫生,2006 ,22( 8 ):975-977.
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