| Objective: Hydroxyurea (HU) is the only antineoplastic used clinically as an RR (Riboneocleotide Reductase) inhibitor for such disease as melanoma, resistant chronic myelocytic leukemia, and inoperable carcinoma of the ovary and so on. It is currently used for an increasing number of symptoms, and with a good clinical effect. However, there have been insufficient studies on male reproductive toxicity of HU, and the systematic reproductive toxicity approaches are still unavailable. In this sudy, we detect genital system toxicity of HU at different points of view which can provid rationale and evidence to use HU safely during the period of clinical treatment.Method: In order to explore the reproductive toxicity of HU, 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 100mg/kg, 200mg/kg ,400mg/kg dosage 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. The weight of testicle and epididymis, the quantity activity and morphology of sperms were examined. Histological of testicle was detected by histopathology technique.The micronucleus rate of early spermatid and Chromosome of primariry spermatocyte was detected. Detection of HU induced DNA single strand breakage in mice germ cell. The purpose of the research is to provide laboratorial data for the study of damage mechanism with HU.Result: 1. 200mg/kg and 400mg/kg HU groups showed statistical significance compared with control groups in variation of body weight (P<0.01). The increment of body weight in 5d shows significance between 200mg/kg, 400mg/kg and control groups(P<0.01). The increment of body weight in 14d show significance between 400mg/kg and control groups(P<0.01). 2. Compared with the control group, significant difference in the weight of testicle and testis index was found in every treatment group (P<0.01). The weight and index of epididymis in 200mg/kg and 400mg/kg group were decreased significantly compared with control (P<0.01). 3. Histological of testicle indicates that HU can lead to a number of trophied tubules and reduce the numbers of germ cell. 4. The spermatozoa count and sperm deformation ratio had significant differentce compared with the negative control group (PO.05, PO.01). The sperm atozoamotility changed significantly between 200mg/kg, 400mg/kg and control groups (P<0.01). 5. The micronucleus rate of early spermatid was increased significantly compared with control (P<0.05, P<0.01). 6. The chromosome aberration rate of primary spermatocytes were significantly higher in 200mg/kg and 400mg/kg groups than those in control (P<0.01). 7. From the comet assay, experimental groups showed statistical significance compared with control group (?<0.01).Conclusion: 1. HU has obviously testicle and epididymis toxicity to male mice. The weight and index of testicle and epididymis were decreased significantly. 2. HU has obviously sperm toxicity to male mice. The spermatozoa count and motility were reduced significantly, and sperm deformation ratio was significantly increased. 3. The results of MNT and chromosome aberrations method indicat that HU is mutagenic activity in male mouse germ cells. 4. SCGE shows that each -dosage group of HU produce DNA lesion to testicle cell. 5. In this study, 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.
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