新型饲料添加剂喹胺醇致突变性及其潜在致癌性预测  

Studies on the Mutagenicity and Teratogenicity of Kuianchun and Its Potential Carcinogenicity Prediction

作　　者：梁剑平[1] 张力[1] 曹随中[2] 周丽霞[1] 周学辉[1] 魏春梅[1] 苗小林[1] 刘宗平[2] 卫增泉 

机构地区：[1]中国农业科学院兰州畜牧与兽药研究所农业部新兽药工程重点实验室,兰州730050 [2]甘肃农业大学,兰州730070 [3]中国科学院近代物理研究所,兰州730000

出　　处：《中国农业科学》2001年第6期679-685,共7页Scientia Agricultura Sinica

基　　金："九五"国家科技攻关项目(96-003-02)

摘　　要：选择Ａｍｅｓ试验、小鼠微核试验和精子畸形试验３种短期试验组合研究了喹胺醇的致突变性，并在获得各 单项试验结果的基础上，利用“致癌性预测和选择试验组合的方法”即 ＣＰＢＳ法对喹胺醇潜在致癌性进行预测。结果表 明：（１）Ａｍｅｓ试验喹胺醇标准掺入不论加与不加Ｓｇ－ｍｉｘ对鼠伤寒沙门氏菌 ＴＡ９８和ＴＡ１００两个标准株都有诱变性，并 有剂量－反应关系。加入 Ｓｇ－ｍｉｘ后，ＴＡ９８和 ＴＡ１００回复突变菌落数均明显下降。（２）小鼠处死前 ３０ｈ和 ６ｈ分别腹腔注 射哇胺醇３０，６０，１２０和２４０ｍｇ／ｋｇ，骨髓嗜多染红细胞（ＰＣＥ）微核率与阴性对照组（５０％ＤＭＳＯ）比较差异均不显著（Ｐ ＞０．０５）。（３）小鼠连续用哇胺醇４５０、７５０、１０００和１５００ ｍｇ／ｋｇ灌胃５ｄ（１次／ｄ），于第３５天处死，精子畸形率与阴性对 照组（２％吐温－８０）比较差异均不显著（Ｐ＞０．０５）。（４）利用ＣＰＢＳ法预测，喹胺醇θ＝０．２３８，初步定为非致癌物，进一步 的结论还需增加试验组合进行确定。Kuianchun is a newly synthesized antibacterial and growth-promoting drug . This paper selected a battery of three short-term tests, including Ames test, microuncleus test and sperm abnormality test to detect the mutagenicity of Kuianchun . The carcinogenicity prediction and battery selection method(CPBS method) was used to determine the probability of carcinogenicity of Kuianchun based upon the results of above mentioned short-term tests. In addition, traditional teratogenic test was selected to study teratogenicity of Kuianchun. Ames test showed that Kuianchun is mutagenic for Salmonella typhimurium strains TA98 and TA100 both in the absense and presence of microsomal metbolic activation system(S9-mix) . However , the mutagenicity was reduced by the addition of S9-mix. In micronucleus test Kuianchun was administered intraperitoneally to male mouse 30 and 6h before they were killed. The result indicated that there was no significant difference on the number of micronucleated polychromatic erythrocytes(PCEs) in the mouse bone marrow induced by Kuianchun compared with the negative control(5000 DMSO)(P>0. 05). In sperm abnomality test, Kuianchun was administered by gastric intubation to male mouse as a suspension in 2oo Tween-80 . The dosage levels were 450, 750, 1000 and 1500mg/kg per day for 5 days. The result indicated that the percentage of abnomal sperms induced by Kuianchun was not significiant(P>0. 05) compared with the negative control. In traditional teratogenic test, Kuianchun was given orally to pregnant mouse at 1/30, 1/20 and 1/15 LD50 during 6-15days of pregnancy period(the LD50 =9000mg/kg). Neither maternal toxicity, embryotoxicity nor teratogenic effects were observed at all test-ed dosages. The probablity of carcinogenicity of Kuianchun is 23. 8%(θ＝0. 238) obtainned by using CPBS method . The result suggested that Kuianchun is a non-carcinogen.

关 键 词：喹胺醇 致突变性 致癌性 遗传毒性 饲养添加剂 兽药安全性 

分 类 号：S816.7[农业科学—饲料科学] S859.82[农业科学—畜牧学]