苯并(a)芘神经行为毒性与CYP1A1基因多态性的关系

Relationship between Neurobehavioral Toxicity of Benzo(a)pyrene and CYP1A1 Gene Polymorphism

[目的]探讨苯并(a)芘的神经行为毒性及其与CYP1A1基因多态性的关系。[方法]从某钢铁公司焦化厂选择200名健康成年男性焦炉工人为研究对象。采用自行设计的问卷,收集研究对象的一般情况资料以及与本研究相关的基本信息;用WHO推荐的神经行为核心测试组合(NCTB)测试焦炉工神经行为功能。收集研究对象的班后尿和肘静脉血,用高效液相色谱法检测尿中1-羟基芘(1-OhP)的水平;聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析CYP1A1基因3′非编码区MspI位点多态性;等位基因特异性扩增(ASA)方法检测CYP1A1基因第7外显子Ile-Val位点多态性。[结果]MspI位点野生型(m1/m1)、杂合型(m1/m2)、突变型(m2/m2)个体间神经行为功能各指标差异无统计学意义(P>0.05);第7外显子Ile-Val位点野生型(Ile/Ile)、杂合型(Ile/Val)、突变型(Val/Val)个体间上述指标比较,突变型(Val/Val)倒序数字跨度得分低于野生型(Ile/Ile),差异有统计学意义(P<0.05)。[结论]苯并(a)芘可引起接触人群神经行为功能损害,可能与CYP1A1第7外显子Ile-Val位点多态性有关。

[ Objective ] To explore the relationship between neurobehavioral toxicity of benzo （a） pyrene and CYP1A1 gene polymorphism. [ Methods ] A total of 200 healthy adult male coke oven workers were selected from a coke plant of a state-owned enterprise in Taiyuan City, and were classified into three exposure categories according to their CYP1A1 gene. The workers＇ general information correlated with the investigation was collected by query and filled in the questionnaire by specially trained investigators. Neurobehavioral core test battery（ NCTB ）recommended by WHO was performed on coke oven workers to test the neurobehavioral changes and the mood state. Blood and urine samples of coke oven workers were collected immediately after their shift at the end of a working day. The level of urinary 1-hydroxypyrene （ 1-OhP ） was measured by high performance liquid chromatography（ HPLC ）. The Msp I gene polymorphism in CYP1A1 3＇ flanking region and the genotypes at Ile-Val site in exon 7 of CYP1A1 were detected by polymerase chain reaction-restriction fragment length polymorphism（ PCR-RFLP ）and allele specific amplification （ ASA ）. [ Results ] No significant differences were found among three genotypes of m1/m1, m1/m2, m2/m2 in Msp I site or of Ile/Ile, Ile/Val, Val/Val of Ile-Val site groups in age, length of service, smoking, drinking and work sites. The scores of dignity span backward with Val/Val gene type were higher than those with Ile/Ile gene type. Other indices of NTCB showed no difference among three gene types of Ile- Val site. All indices of NTCB showed no difference among three gene type of Msp I site. The level of urinary 1-OhP of Val/Val was significantly higher than Ile/Ile wild homozygote. However, there was no statistically significant difference on concentration of urinary 1-OhP among three genotype m1/m1, m1/m2 and m2/m2. [ Conclusion ] The changes of neurobehavioral function by occupational benzo（a） pyrene exposure might be related with the CYP1A1 gene polymorphism in the seventh extron.