动式吸入苯并[a]芘染毒途径建立小鼠肺癌模型  

Establishment of mouse lung cancer model induced by benzo[a]pyrene dynamic inhalation exposure

作　　者：邹旋 付英斌[1] 吴德生[1] 刘建军[1] 肖云军[1] 黄海燕[1] Zou Xuan;Fu Yingbin;Wu Desheng;Liu Jianjun;Xiao Yunjun;Huang Haiyan(Shenzhen Center for Disease Control and Prevention,Shenzhen 518055,China)

机构地区：[1]深圳市疾病预防控制中心,深圳518055

出　　处：《卫生研究》2020年第3期486-490,共5页Journal of Hygiene Research

基　　金：广东省自然科学基金(No.2019A1515011080);深圳市基础研究专项(No.20190801152345759)。

摘　　要：目的采用动式吸入苯并[a]芘(B[a]P)染毒途径建立小鼠肺癌模型。方法选用96只SPF级C57BL/6J小鼠,18~20 g,雌雄各半,随机分为实验组和对照组,每组48只。实验组动式吸入染毒途径给予10.0μg/m^3B[a]P,6 h/d、5天/周,对照组给予等量溶剂二甲基亚砜(dimethyl sulfoxide,DMSO)处理。于染毒第13周和25周,随机抽取24只小鼠处死,解剖肺脏并观察肺癌形成情况。染毒期间,每周采用活性炭管法采集染毒柜内气体,气相色谱质谱仪分析B[a]P含量;采用竞争性酶联免疫吸附法(ELISA)测定小鼠全血中(7R,8S)-二羟基-(9S,10R)-环氧-7,8,9,10-四氢苯并[a]芘(BPDE)-DNA加合物含量,检测小鼠体内B[a]P的暴露剂量。结果动式吸入染毒柜内的B[a]P浓度稳定在(12.794±0.518)μg/m^3,实验组染毒13周与染毒25周动物体内BPDE-DNA含量的差异无统计学意义;染毒25周后,实验组肺癌形成率明显高于对照组(P<0.05),且实验组雌性小鼠肺癌发病率(100.0%)明显高于雄性(58.3%)(P<0.05)。结论成功建立苯并[a]芘诱导的小鼠肺癌模型。OBJECTIVE To establish a mouse lung cancer model induced by benzo[a]pyrene(B[a]P)dynamic inhalation exposure.METHODS A total of 96 C57 BL/6 J mice weighing 18 to 20 g were randomly divided into the control group(n=48)and the experimental group(n=48),male and female in half.The experimental group was treated with 10.0μg/m^3 BaP for 13 weeks or 25 weeks(6 h per day and 5 days per week)by dynamic inhalation exposure,while the control group was given dimethyl sulfoxide(DMSO).The 13 weeks or 25 weeks after B[a]P exposure,24 mice were sacrificed and their lung tissues dissected and observed for tumor formation.During B[a]P exposure,the gas in the poisoning cabinet was collected by the active carbon tube method regularly,and the concentration of B[a]P in the poisoning cabinet was analyzed by gas chromatography mass spectrometer,and the(7 R,8 S)-dihydroxy-(9 S,10 R)-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene(BPDE)-DNA adduct content in the whole blood of mice was determined by ELISA.RESULTS Concentration of B[a]P in the dynamic inhalation cabinet was stable at(12.794±0.518)μg/m^3.There was no significant difference in the BPDE-DNA content in the experimental objects between 13 weeks and 25 weeks after B[a]P exposure(P>0.05).After 25 weeks of B[a]P exposure,the lung cancer formation rate in the experimental group was significantly higher than that in the control group(P<0.05),the tumor formation rate of female mice was up to 100%.CONCLUSION The mice lung cancer model induced by B[a]P dynamic inhalation exposure was established successfully.

关 键 词：苯并[A]芘 C57BL/6J小鼠 肺癌 吸入染毒 大气污染 

分 类 号：X513.031[环境科学与工程—环境工程] R734.2[医药卫生—肿瘤]