摘要
目的研究五氯酚钠（Na PCP）的发育毒性和遗传毒性,为保护生态环境和人类健康提供依据。方法采用斑马鱼胚胎发育试验、斑马鱼卵p53基因诱变性试验、蚕豆根尖细胞微核试验和鼠伤寒沙门氏菌回复突变试验研究Na PCP的发育毒性和遗传毒性。结果 Na PCP对斑马鱼卵的96 h半数致死浓度（LC50）为3.81μL/L;斑马鱼胚胎发育试验结果显示,在0.5~2.5μL/L范围内,随着Na PCP浓度增加,斑马鱼胚胎畸变率和死亡率上升,胚胎孵化率下降,Na PCP诱发的胚胎畸变类型主要为脊椎弯曲、心包囊肿和骨骼畸形等;斑马鱼卵p53基因诱变性试验结果显示,在0.4μL/L Na PCP中连续暴露24 h后,斑马鱼p53基因的第49、87和158位密码子分别发生AAT→AAG、ACA→ACG和GCG→GCA突变,导致p53蛋白发生Asn→Lys变异;细胞微核试验结果显示,Na PCP对蚕豆根尖细胞具有致微核性,其0.20 mg/L和1.00 mg/L剂量组微核率分别为（7.0±2.2）‰和（10.3±5.2）‰,均高于阴性对照组的（1.8±1.4）‰（P〈0.01）;鼠伤寒沙门氏菌回复突变试验结果为阴性。结论 Na PCP是一种遗传毒性物质,可导致染色体畸变和基因点突变,对胚胎和生殖细胞有致畸和致突变作用。
Objective To investigate teratogenicity on the zebrafish embryo and genetoxicity induced by Sodium Pentachlorophenate（ Na PCP）,and to provide suggestions for protecting the environmental safety and human health.Methods Zebrafish embryonic development test,p53 gene in zebrafish eggs mutagenicity test,Vicia Faba Micronucleus Test and Ames test were used in the studies. Results The results of zebrafish embryonic development test showed that Na PCP increased embryonic 120 hpf teratogeny rates and 120 hpf death rates and decreased embryonic 120 hpf hatching rates in concentration of 0. 5- 2. 5 μL / L,with significant teratogenic effect on the embryo. The rates of embryo abnormity increased with the exposure time and concentration. Sequence analysis showed that Na PCP exposure group zebrafish p53 gene had mutated at the concentration of 0. 4 μL / L. The base substitution of AAT → AAG at codon 49,ACA → ACG at codon 87 and GCG→GCA at codon 158 were detected by PCR- directed sequencing. This may result in the Asn→Lys of expressed p53 protein. As compared with control group,0. 2 mg / L,1. 0 mg / L dosage of Na PCP could induce an extremely significant increase in micronucleus frequency of vicia faba root tip cells and had a certain dose- effect relationship. Ames test was negative. Conclusion Na PCP could delay embryonic development and even cause embryonic lethality and induce abnormality in zebrafish. Na PCP had certain genetoxicity.
出处
《预防医学》
2016年第11期1081-1086,1090,共7页
CHINA PREVENTIVE MEDICINE JOURNAL
基金
浙江省科学技术厅实验动物科技计划项目(2014C37032)
关键词
五氯酚钠
发育毒性
遗传毒性
Sodium pentachlorophenate
Development toxicity
Genetoxicity
