CAJ | 학술논문

目的探讨氯乙烯(VCM)致染色体损伤与DNA修复基因和代谢酶基因多态间的关系.方法收集上海某化工厂402名VCM接触工人健康体检资料、人口学资料(年龄和性别)、生活方式(吸烟、饮酒)和职业接触等因素,评估个人VCM累积接触剂量并分组.采集静脉血3 ml,采用外周血淋巴细胞胞质分裂阻滞微核试验(CBMN)检测染色体损伤,采用聚合酶链式反应(PCR)检测GSTT1、GSTM1基因缺失情况,采用PCR-限制性片段长度多态性技术(RFLP)检测其他基因多态.结果多元Poisson回归分析结果表明,中(4000～40000 mg)、高(＞40000 mg)VCM接触剂量组染色体损伤的风险明显高于低剂量组,调整后的FR值分别为1.19(1.06～1.34)和1.20(1.06～1.38),差异有统计学意义(P值分别为0.003和0.01);携带CYP2E1和XRCC1 Arg280His突变型基因的个体微核率明显高于野生型个体,调整后的FR值分别为1.12(1.02～1.23)和1.13(1.02～1.25),差异有统计学意义(P值均为0.02);携带GSTP1Val/Val和ALDH2 Glu/Glu基因型个体微核率明显高于其他基因型个体,调整后的FR值分别为0.74(0.59～0.94)和0.87(0.79～0.95),差异有统计学意义(P值分别为0.01和0.003).结论 VCM致染色体损伤与VCM累积接触剂量增高及GSTP1 Val/Val、CYP21E1 c1c2/c2c2、ALDH2 Glu/Glu、XRCC1 280His/His 或Arg/His基因型多态性等因素有关.开展VCM致染色体损伤与遗传易感性方面的研究,有助于VCM致癌机制的阐明,而研究中易感性多态位点的发现也可以为识别易感人群提供理论依据.
목적 탐토록을희(VCM)치염색체손상여DNA수복기인화대사매기인다태간적관계.방법 수집상해모화공엄402명VCM접촉공인건강체검자료、인구학자료(년령화성별)、생활방식(흡연、음주)화직업접촉등인소,평고개인VCM루적접촉제량병분조.채집정맥혈3 ml,채용외주혈림파세포포질분렬조체미핵시험(CBMN)검측염색체손상,채용취합매련식반응(PCR)검측GSTT1、GSTM1기인결실정황,채용PCR-한제성편단장도다태성기술(RFLP)검측기타기인다태.결과 다원Poisson회귀분석결과표명,중(4000～40000 mg)、고(＞40000 mg)VCM접촉제량조염색체손상적풍험명현고우저제량조,조정후적FR치분별위1.19(1.06～1.34)화1.20(1.06～1.38),차이유통계학의의(P치분별위0.003화0.01);휴대CYP2E1화XRCC1 Arg280His돌변형기인적개체미핵솔명현고우야생형개체,조정후적FR치분별위1.12(1.02～1.23)화1.13(1.02～1.25),차이유통계학의의(P치균위0.02);휴대GSTP1Val/Val화ALDH2 Glu/Glu기인형개체미핵솔명현고우기타기인형개체,조정후적FR치분별위0.74(0.59～0.94)화0.87(0.79～0.95),차이유통계학의의(P치분별위0.01화0.003).결론 VCM치염색체손상여VCM루적접촉제량증고급GSTP1 Val/Val、CYP21E1 c1c2/c2c2、ALDH2 Glu/Glu、XRCC1 280His/His 혹Arg/His기인형다태성등인소유관.개전VCM치염색체손상여유전역감성방면적연구,유조우VCM치암궤제적천명,이연구중역감성다태위점적발현야가이위식별역감인군제공이론의거.
Objective To explore the association between chromosomal damage induced by vinyl chloride monomer (VCM) and polymorphisms of xenobiotic metabolism genes and DNA repair genes.Methods Cytokinesis-block micronucleus (CBMN) test was performed to detect chromosomal damage in peripheral lymphocytes of 402 VCM-exposed workers.Multiplex PCR was used to simultaneously amplify GSTM1 and GSTT1 genes, other genetic polymorphisms were performed using a PCR-RFLP technique.Results Multiple (adjusted) Poisson regression analysis showed that mean MN frequencies were significantly elevated for the intermediate (4000～40000 mg) and high (＞40000 mg) exposure groups as compared with the low exposure group (P=0.003and 0.03, respectively).For genetic polymorphisms, the exposed workers with CYP2E1 or XRCC1 Arg280His variance showed a higher CBMN frequency than their wild-type homozygous counterparts (P=0.02); so did the workers with GSTP1 105Val/Val genotype or ALDH2 504Glu/Glu genotype than those with a combination of othergenotypes (P=0.01and 0.003, respectively).Conclusion Ourfindings reveal that cumulative exposure doseof VCM and common genetic variants in genes,such as GSTP1,CYP2E1, ALDH2, XRCC1 Arg280His genotypes, are the major factors that modulate MN induction in VCM- exposed workers.Further study to investigate the relationship between individual characteristics and genetic susceptibility to VCM-caused chromosome damage is warranted,it is helpful for us to understand the mechanism of VCM metabolism, to find the biomarkers of susceptibility and to recognize the susceptible individuals in the primary prevention of VCM-caused damage.