摘要
目的评价羟基脲(Hydroxyurea,HU)对睾丸细胞DNA损伤作用,为研究HU生殖系统损伤机制提供实验室数据,并为临床治疗过程中安全使用HU提供理论基础和依据。方法以雄性小鼠经腹腔注射建立动物模型,HU剂量组分别为100、200和400 mg/kg,并设对照组,连续给药5 d,首次给药14 d后,用单细胞凝胶电泳技术,评价HU对雄性小鼠生殖系统的影响。结果彗星实验结果显示,HU各剂量组中反映睾丸细胞DNA损伤的指标与对照组相比均明显增高(P<0.01),且DNA受损率随HU剂量增高而增高(P<0.01)。结论HU对小鼠睾丸细胞DNA有持续损伤作用,并抑制其损伤的修复。临床上大量和长期使用HU时,应充分考虑其生殖毒性作用的远期影响或采取一定的抑制措施。
Objective To detect genital system toxicity of HU which can provid rationale and evidence to use HU safely during the period of clinical treatment. Methods Male mice were taken as subjects. The animal model was made by intraperitioneal injection with HU for successive five days, and the mice were divided into 4 groups, such as 100, 200,400 mg/kg and the control which was made by intraperitioneal injection with normal saline for successive five days. The mice were sacrificed on the 14th day after the first injection. Detection of HU-induced DNA single strand breakage in mice germ cell by SCGE. Results From the comet assay, experimental groups showed statistical significance compared with control group（ P 〈 0.01 ） ,and significant dose-reaction relationship of HU--induced DNA lesion to testicle cell（ P 〈 0.01 ）. Conclusion HU can result in obviously adverse effects in the reproductive system of male mice. We have to pay more attention to adverse effects of HU in the long-term or take effective measures to control them in clinical.
出处
《毒理学杂志》
CAS
CSCD
北大核心
2009年第2期118-121,共4页
Journal of Toxicology
基金
山西医科大学基础医学院"学科研究方向建设基金"(20040708)
关键词
羟基脲
生殖毒性
单细胞凝胶电泳技术
Hydroxyurea （HU）
Reproduction toxicity
Single cell gel electrophoresis （SCGE）
