新型饲料添加剂喹胺醇致突变性及其潜在致癌性预测

 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。     

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

Kuianchun is a newly synthesized antibacterial and growth-promoting drug. This paper selected a battery of three short-term tests, including Ames test, micronucleus 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 shortterm tests mentioned above. In addition, traditional teratogenic test was selected to study teratogenicity of Kuianchun. In Ames test, Kuianchun showed mutagenic for Salmonella typhimurium strains TA98 and TA100 in the absence and presence of microsomal metabolic activation system (S9-mix). However, the mutagenicity was reduced by the addition of S9-mix. In micronucleus test, Kuianchun was administered intra-peritoneally to male mouse 30 hours and 6 hours before they were killed respectively. 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 contrast (50% DMSO) (P ＞ 0.05). In sperm abnormality test, Kuianchun was administered through a gastric incubation to male mouse as a suspension in 2% Tween-80. The dosage levels were 450, 750, 1000 and 1500mg/kg per day for 5 days. The result indicated that the percentage of abnormal sperms induced by Kuianchun was not significant compared with the negative contrast (P＞0.05). In traditional teratogenic test, Kuianchun was given orally to pregnant mouse at 1/30,1/20 and 1/15 LDs0 during 6 - 15days of pregnancy period (the LD50 = 9000mg/kg). No toxicity was found either on mother and embryo in mouse, and teratogenic effects were also not observed at all tested dosages. The probability of carcinogenicity of Kuianchun is 23.8 % (θ = 0.238). The result demonstrated that Kuianchun is a non-carcinogen.