通过体内多终点遗传毒性综合评价体系探索双酚AF的遗传毒性  

Genotoxicity evaluation of bisphenol AF by multi-endpoint genotoxicity evaluation system in vivo

作　　者：张静 朱霞 苗野萩 唐欣瑶 张立实 王娟 陈锦瑶 ZHANG Jing;ZHU Xia;MIAO Ye-qiu;TANG Xin-yao;ZHANG Li-shi;WANG Juan;CHEN Jin-yao(West China School of Public Health and West China Fourth Hospital,Sichuan University,Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province,Chengdu Sichuan 610041,China;Department of Clinical Nutrition,The Second People's Hospital of Yibin,Yibin Sichuan 644002,China)

机构地区：[1]四川大学华西公共卫生学院/华西第四医院,四川省食品安全监测与风险评估重点实验室,四川成都610041 [2]宜宾市第二人民医院临床营养科,四川宜宾644002

出　　处：《毒理学杂志》2023年第2期166-170,F0003,共6页Journal of Toxicology

基　　金：四川省科技厅项目(2022JDJQ0026);四川大学创新火花项目(2018SCUH0005)。

摘　　要：目的研究旨在使用体内多终点遗传毒性整合方案(基于流式细胞术的Pig-a基因突变试验+流式微核试验+彗星试验)探索双酚AF(Bisphenol AF,BPAF)3 d重复暴露的体内遗传毒性。方法30只5~6周龄SD雄性大鼠随机分为5组,每组6只。包括N-乙基-N-亚硝基脲阳性对照组(40 mg/kg)、PBS溶剂对照组(pH=6.0)、玉米油溶剂对照组、BPAF低剂量组(_(0.5μg/kg))和BPAF高剂量组(_(50μg/kg))。连续3 d经口灌胃。在试验前一天、第14天和第28天进行Pig-a基因突变试验;在试验前一天和第4天进行外周血微核试验;在试验第4天进行外周血彗星试验。结果Pig-a基因突变试验结果显示BPAF未诱导成熟红细胞(D14:P_(0.5μg/kg)=0.963,P_(50μg/kg)=0.873;D28:P_(0.5μg/kg)=0.217,P_(50μg/kg)=0.277)和网织红细胞(D14:P_(0.5μg/kg)=0.955,P_(50μg/kg)=0.156;D28:P_(0.5μg/kg)=0.410,P_(50μg/kg)=0.990)突变率明显升高;微核试验结果显示BPAF未诱导网织红细胞微核率明显变化(P_(0.5μg/kg)=0.367,P_(50μg/kg)=0.891);彗星试验中双酚AF高剂量组尾部DNA百分含量明显升高(P=0.038)。结论本试验条件下,BPAF 3 d重复暴露可诱导DNA损伤,其遗传毒性需要进一步探讨。Objective This study aimed to explore the in vivo genotoxicity of 3-day repeated exposure to bisphenol AF using an in vivo multi-endpoint genotoxicity integration protocol(Pig-a assay+micronucleus test+comet assay).Methods The Sprague-Dawley(SD)male rats(n=30)aged 5-6 weeks were randomly divided into 5 groups(6 rats per group),that is,N-ethyl-N-nitrosourea positive control group(40 mg/kg),PBS solvent control group(pH=6.0),corn oil solvent control group,bisphenol AF low-dose group(0.5μg/kg),and bisphenol AF high-dose group(50μg/kg).Treatments were administered by oral gavage to male SD rats for 3 consecutive days.Pig-a gene mutation test was performed on the day before the experiment,the 14th day,and the 28th day respectively.The peripheral blood micronucleus test was performed on the day before the experiment and the 4th day,respectively.The peripheral blood comet test was performed on the 4th day of the experiment.Results The Pig-a gene mutation test showed that bisphenol AF did not induce the mutation rate of mature erythroeyte(D14:Po.w/ke=0.963,Pow/ke=0.873;D28:Po.+/g=0.217,Pso uw/ke=0.277)and retiuloeytes(D14:Pos wa=.955,sow=.156;28:eas wue=-.410,sowa=.90)to inereasesigifcanly heresul of microuclustest showed that bisphenol AF did not induce signifiant changes in the micronucleus rate of reticulocytes(Po.s ug/kg=0.367,Pso/kg=0.891).The percentage of tail DNA was significantly increased in the bisphenol AF high-dose group in the comet assay(P=0.038).Conclusion Under the conditions of this study,repeated exposure to bisphenol AF for 3 days can induce DNA damage,and its genotoxicity needsto befurther investigated.

关 键 词：双酚AF 体内遗传毒性 Pig-a基因突变试验 微核试验 彗星试验 

分 类 号：R114[医药卫生—卫生毒理学] R99[医药卫生—公共卫生与预防医学]