甲氧化三丁基锡的急性毒性和遗传毒性研究  

Acute toxicity and genetic toxicity of tributyltin methoxide

作　　者：刘文斌[1] 杨录军 李永红[1] 刘晋祎[1] 曹佳[1] 敖琳[1] 

机构地区：[1]第三军医大学军事预防医学院毒理学研究所,重庆400038 [2]重庆市人口与计划生育科学技术研究院,重庆400020

出　　处：《癌变．畸变．突变》2012年第5期335-339,共5页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金：国家重点基础研究发展计划(2011CB503705)

摘　　要：目的:研究甲氧化三丁基锡(tributyltin methoxide,TBTMO)对小鼠的急性毒性和遗传毒性。方法:选取昆明种小鼠110只,随机分为11组(TBTMO 420、286、194、180、132、90、73、61、41.5、28 mg/kg及阴性对照组),一次性灌胃给药进行急性毒性测试;另取昆明种小鼠50只随机分成5组(TBTMO 80、40、20 mg/kg组,阴性对照组和阳性对照组),各剂量组和阴性对照组均连续给药2 d,阳性对照组连续给药5 d,均连续观察35d,处死小鼠取双侧附睾制片进行精子畸形试验;并取昆明种小鼠50只随机分成5组(TBTMO 80、40、20 mg/kg组,阴性对照组和阳性对照组),灌胃给药30 h后处死小鼠取胸骨骨髓进行微核试验;取GFP转基因小鼠50只随机分成5组(TBTMO 80、40、20 mg/kg组,阴性对照组和阳性对照组),收集每只小鼠的脾淋巴细胞进行hprt基因突变试验。然后用不同浓度TBTMO(69.4、48.6、34.0、23.8、16.6、0μg/ml)分别处理中国仓鼠肺成纤维细胞(Chinesehamster lung,CHL)进行染色体畸变试验;用不同浓度TBTMO(每皿5×10~5、5×10~4、5×10~3、5×10~2、50、5、0.5、0.05、5×10^-3、5×10^-4μg)分别处理TA97、TA98、TA100、TA102 4种菌株进行Ames试验。结果:TBTMO对小鼠的半数致死量(LD_(50))为98 mg/kg。与阴性对照组比较,TBTMO可致小鼠精子畸形(P<0.05或P<0.01),且有剂量依赖趋势,其余4项遗传毒性试验结果均为阴性。结论:在本实验条件下,TBTMO对小鼠的急性经口毒性属于中等毒性,可能具有一定的遗传毒性。OBJECTIVE：To investigate the acute toxicity and genetic toxicity of tributyltin methoxide （TBTMO）.METHODS：A total of 110 Kunming mice were randomly divided into 11 groups,then treated orally with various doses of TBTMO（420,286,194,180,132,90,73,61,41.5 and 28 mg/kg） to perform acute toxicity test. A total of 50 Kunming mice were randomly divided into 5 groups（TBTMO 80,40,20 mg/kg,positive control and negative control）.Positive control was treated for five consecutive days.Other four groups were treated for two days.These animals were killed 35 d later,and their bilateral epididymis were removed for sperm shape abnormality test.Another 50 Kunming mice were randomly divided into 5 groups and treated as above mentioned.The animals were killed 30 h after gavage with TBTMO,and their chest bone marrow fluid were obtained for bone marrow mieronueleus test.Another 50 GFP transgenic mice were randomly divided into 5 groups and treated as above.The animals were killed and their spleen lymphocyte was used for hprt gene mutation test.Various doses of TBTMO（69.4,48.6,34.0.23.8,16.6 and 0μg/ml） were used to treat Chinese hamster lung（CHL） cell for chromosome aberration test.Different doses of TBTMO （5×10^5,5×10^4,5×10^3,5×10^2,50,5,0.5,0.05,5×10^-3,5×10^-4μg/dish） were used to deal with TA97, TA98,TA100,TA102 strains for Ames test.RESULTS：The LD_（50） of TBTMO in mice was 98 mg/kg.TBTMO could induce sperm abnormality in a dose-dependent manner（P 0.05）.The other four tests showed negative results. CONCLUSION：Under our experimental conditions,TBTMO was classified as moderately-toxic substance.It may produce genetic toxicity.

关 键 词：甲氧化三丁基锡 急性毒性 遗传毒性 

分 类 号：Q355[生物学—遗传学]