Effect Of CYP1A1, GSTT1 And GSTM1 Polymorphismis On Frequencies Of Micronucleated Binucleated Cells Among Residents From An Electronic Waste Dismantling Site

Electronic waste (e-waste) is one kind of solid waste. A large amount of e-waste increased rapidly all over the world. If they are treated improperly, certain chemicals such as polybrominated diphenyl ethers (PBDEs), heavy metals and polychlorinated biphenyl (PCB) discharging from e-waste can cause pollution of the surrounding environment of e-waste place and threaten human health.PBDEs as flame retardants have been used in polymeric materials. Concern on PBDEs has been attracted as the new pollutants. They can exist persistently in the environment and accumulate in the organisms. Recent years, detected levels of PBDEs showed an increasing trend, in the biological samples including human serum, breast milk and adipose tissue, which are reported by many countries in the world. Evidence suggests that PBDEs exposure could disturb endocrine function, and impact on functions of liver, nervous system, reproduction, and growth in the organisms. However, the mechanisms of adverse effects of PBDEs on the organisms are unclear, and few studies related to adverse effetcts of PBDEs on human.Most of environmental chemicals that enter the organisms, in general, are metabolized to intermediates or final metabolic products, through the biotransformation reactions catalyzed by phaseⅠand/or phaseⅡenzymes. Some of the metabolic products can cause DNA damage. Both Cytochrome P450 1A1 (CYP1A1) and glutathione S-transferases (GST) belong to phaseⅠand phaseⅡenzymes, respectively. Their activities are very important because the activities can influence the metabolism processes of toxic chemicals in the organisms. Previous studies indicated that polymorphisms in metabolic enzyme genes are basis of the inherited susceptibility of population to some diseases.In this study, we investigated the effects of the pollutants from the e-waste dismantling site on human health, and analysed the association of polymorphisms in CYP1A1, GSTT1 and GSTM1 genes with content of DNA damage in peripheral blood lymphocytes among subjects in the e-waste dismantling site.PartⅠ: Association between serum polybrominated diphenyl ethers and thyroid-stimulating hormone among the workersWe recruited 23 workers who dismantled and"recycled"electronic goods from a decade-long e-waste recycling site in southeast China (as exposed group). Another 26 farmers from one village located 50 km away from the e-waste site without other pollutions (as control group). The level of serum thyroid-stimulating hormone (TSH) and uriary 8-hydroxy-2'-deoxyguanosine (8-OHdG) level were analyzed by the chemiluminescent microparticle immunoassay and high performance liquid chromatograph-electrochemistry (HPLC-EC), respectively. We found that levels of sera PBDEs (median: 382 ng/g lipid weight) was 2.4 times that one in the control (median: 158 ng/g lipid weight, P<0.05). The serum TSH level in the exposed group (median: 1.79μIU/ml) also was significantly higher than that in the control group (1.15μIU/ml, P<0.01). In the studied population, a negative correlation between the serum malondialdehyde (MDA) level and the serum TSH level was observed (r = -0.454, P<0.01). In contrast, a positive correlation between the serum supreroxide dismutases (SOD) activity and with the serum TSH level (r = 0.340,P<0.05) in the studied population. In addition, we further analyzed the factor relating to the serum TSH level. The findings showed that both a history of engaging in e-waste (OR = 6.12; 95% confidence interval (C.I): 1.58-23.72, P<0.01) and female (OR = 4.35; 95% C.I: 1.06-17.80, P<0.05) were risk factors for the elevanted TSH level. They were independent predictors of serum TSH level.PartⅡ: Effect of CYP1A1, GSTM1 and GSTT1 polymorphisms on the frequencies of micnucleated binnucleated cells in peripheral blood lymphocytes among residents in the e-waste dismantling siteIn this study we recuited 58 residents from the e-waste dismantling site (as exposed group) and 80 residents from the village (as control group). The personal information on age, sex, smoking, alcohol status and history of engaging in e-waste were collected using a questionnaire. Analysis of genotypes CYP1A1, GSTM1 and GSTT1 were performed using the PCR-RFLP method or the multiplex PCR method. The frequencies of MNed BNC in peripheral blood lymphocytes were detected using the cytokinesis-block micronucleus (CBMN) assay. It was used the analysis of Bonferroni correction for multiple comparisons with adjustment for age, sex, cigarettes per day, alcohol status and the occupational history. We found that no significantly difference in the distributions of genotypes of CYP1A1, GSTM1 and GSTT1 between the two groups. Further analysis showed that the frequencies of MNed BNC in the exposed group were significantly higher than in the control in subjects with the CYP1A1 wild-type homozygous (AA) or heterozygous (Aa), GSTT1 homozygous gene deletion (null) genotypes of the metabolic enzyme genes (data was not shown). In control group only subjects with the CYP1A1 homozygous rara allele genotype (aa) had the elevated frequencies of MNed BNC (mean±SD: 1.44±1.36‰), compared with subjects with wild-type homozygous (AA) or heterozygous (Aa) genotypes (mean±SD: 1.11±1.49‰, P<0.05). The possible reason is the polymorphisms of other metabolic enzymes genes or DNA repaire genes which were not investigate in our study may have the potential influence on the formation of the micronuclei in peripheral blood lymphocytes of humans. But it need further to be determined in larger population.