促性腺激素对大鼠网织红细胞遗传毒性作用的体内评估。
In vivo evaluation of the genotoxic effects of gonadotropins on rat reticulocytes.
作者信息
Duran Bulent, Koc Onder, Ozdemirci Safak, Topcuoglu Ata, Ozdemir Ozturk
机构信息
Department of Obstetrics and Gynecology, Faculty of Medicine, Abant Izzet Baysal University, Bolu, Turkey.
Department of Obstetrics and Gynecology, Simav Government Hospital, Kütahya, Turkey.
出版信息
Curr Ther Res Clin Exp. 2011 Apr;72(2):60-70. doi: 10.1016/j.curtheres.2011.03.003.
BACKGROUND
Gonadotropins, as ovulation-inducing drugs, have been used widely to treat infertility. An epidemiologic correlation between infertility therapy and ovarian cancer development has been reported. However, the effect of gonadotropins in the formation of reproductive tract cancers is controversial.
OBJECTIVE
The aim of the study was to determine the in vivo genotoxic effects of gonadotropins on rat reticulocytes.
METHODS
In this prospective, randomized, controlled study, rats were randomly assigned to 1 of 5 groups. The calculated rat doses of 0.65 human menopausal gonadotropin (hMG), 0.95 hMG, 0.65 follitropin beta (FB), 0.95 FB, or normal saline (control group) were injected, respectively. These calculated rat doses (U/g) are based on average human gonadotropin doses of 150 and 225 IU/d for a 70-kg woman given in 2-mL saline (the control group received 2 mL of saline). Injections were administered once per day for 5 days, followed by 5 days of rest. Each treatment was repeated for 6 estrus cycles in the rats for a total of 12 estrus cycles. Six months after the last day of the 12(th) cycle, the rats were euthanized. Bone marrow tissues were removed, and pluripotent reticulocyte cells with micronuclei, nuclear buds, and binuclear abnormalities were analyzed using an in situ micronuclei assay under light microscopy. The proportion of micronucleated cells, cells with anaphase bridge, nuclear buds, and other nuclear abnormalities were measured.
RESULTS
The number of cells with nuclear buds and binuclear abnormalities in the hMG 225 and FB 225 groups was significantly higher (P < 0.05) than that from the hMG 150, FB 150, and control groups in the cytogenetic analysis of bone marrow stem cells. An increased rate of genotoxicity in all gonadotropin groups versus that of placebo was found.
CONCLUSION
In rats, the micronucleus genotoxicity assay suggests a dose-dependent gonadotropin effect on genomic instability in bone marrow stem cells in vivo.
背景
促性腺激素作为促排卵药物，已被广泛用于治疗不孕症。已有报道称不孕症治疗与卵巢癌发生之间存在流行病学关联。然而，促性腺激素在生殖道癌症形成中的作用存在争议。
目的
本研究旨在确定促性腺激素对大鼠网织红细胞的体内遗传毒性作用。
方法
在这项前瞻性、随机、对照研究中，将大鼠随机分为5组中的1组。分别注射计算得出的大鼠剂量的0.65人绝经期促性腺激素（hMG）、0.95 hMG、0.65促卵泡素β（FB）、0.95 FB或生理盐水（对照组）。这些计算得出的大鼠剂量（U/g）基于70 kg女性平均人促性腺激素剂量150和225 IU/d，溶于2 mL生理盐水中（对照组接受2 mL生理盐水）。每天注射1次，共注射5天，随后休息5天。每种处理在大鼠中重复6个发情周期，共12个发情周期。在第12个周期的最后一天后6个月，对大鼠实施安乐死。取出骨髓组织，在光学显微镜下使用原位微核试验分析具有微核、核芽和双核异常的多能网织红细胞。测量微核细胞、具有后期桥的细胞、核芽和其他核异常的比例。
结果
在骨髓干细胞的细胞遗传学分析中，hMG 225和FB 225组中具有核芽和双核异常的细胞数量显著高于hMG 150、FB 150和对照组（P < 0.05）。发现所有促性腺激素组的遗传毒性发生率均高于安慰剂组。
结论
在大鼠中，微核遗传毒性试验表明促性腺激素对体内骨髓干细胞基因组不稳定性具有剂量依赖性作用。
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