新型含铜避孕复合材料的遗传毒性评估及体内DNA损伤修复——含铜材料遗传学毒性

Evaluation of Genotoxicity and Repair of DNA Damage in a Novel Copper-Containing Contraceptive Composites—Genotoxicity of Copper-Containing Composite

摘要: 目的：评估新型含铜避孕复合材料(聚乙烯醇，二氧化硅纳米颗粒高分子复合材料)在哺乳动物体内外遗传毒性及损伤修复能力。方法：采用彗星实验测定细胞DNA损伤程度，含铜复合材料50%，25%浸提液处理后以及继续培养3小时后检测细胞内活性氧类物质(Reactive Oxygen Species, ROS)荧光强度，测定染毒后小鼠血浆中超氧化物歧化酶活力(superoxidantase, SOD)。结果：① 细胞经两个不同含铜复合材料浸提液浓度处理3小时后，细胞DNA受损，继续培养3小时后，细胞受损程度有所增加，细胞内ROS含量在处理后和继续培养3小时平均荧光强度与阴性对照组相比有明显升高；② 雌性小鼠于染毒后第2、3、4天血细胞DNA损伤程度最严重，第5天DNA损伤有明显降低，血浆内SOD含量第3天达到高峰。雄性小鼠于染毒后第4天DNA损伤最严重，第6天明显降低，SOD含量于第4天和第7天显著升高。结论：虽然含铜材料在体外可以使细胞DNA受损，体内的损伤修复机制可以使受损细胞修复并抑制铜离子进一步对细胞的损伤，SOD在损伤修复中可能发挥一定的作用。

Abstract: Objects: To evaluate the genotoxicity and damage repair ability of novel copper-containing con-traceptive composites (polyvinyl alcohol and silica nanoparticle composites) in mammals. Methods: The degree of DNA damage was estimated by comet assay. The fluorescence intensity of in-tracellular reactive oxygen species (ROS) was detected after treatment with 50% and 25% cop-per-containing composite leaching solution, and further cultured for 3 hours. The Superoxide dismutase activity (SOD) in plasma was measured by WST. Results: ① Cells DNA were damaged after treatment with three different concentrations of copper-containing composite extracts for 3 hours. After 3 hours of continuous culture, the degree of cell damage was increased and the intra-cellular ROS was significantly increased compared with the negative control group; ② In female mice, the DNA damage degree was the most serious on the 2nd, the 3rd and the 4th day after treatment and significantly reduced on the 5th day. The content of SOD in plasma reached its peak on the 3rd day. The DNA damage degree of male mice was the most on the 4th day after the infec-tion, and obviously decreased on the 6th day. The content of SOD increased significantly on the 4th day and the 7th day. Conclusions: Although copper-containing materials can damage cellular DNA in vitro, the mechanism of damage repair in vivo can repair part damaged cells and inhibit further copper damage on cells with SOD playing a role in injury repair.