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首页> 外文期刊>The Journal of toxicological sciences >An unusual phenotypic and genotypic expression in F2 generation following one stage zidovudine exposure during pregnancy and lactation- an experiment in mice.
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An unusual phenotypic and genotypic expression in F2 generation following one stage zidovudine exposure during pregnancy and lactation- an experiment in mice.

机译：齐多夫定在妊娠和哺乳期经历了一个阶段的暴露后，在F2代中出现了异常的表型和基因型表达-这是一项小鼠实验。

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摘要

Zidovudine (3'-Azido-2', 3'-dideoxythymidine, AZT, ZDV) is routinely used as one of the component of antiretroviral therapy to prevent transmission of the HIV infection from mother to child. The drug, when given during pregnancy can give rise to myriad toxicities as reported in previous studies on human, animal and in-vitro experiments. The present study was an attempt to explore the Zidovudine teratogenesis in F1 and F2 generation of mice following initial maternal exposure to Zidovudine during pregnancy, through delivery and lactation. The F1 generation actually would have got the exposure during embryonic development and infant stages. Pregnant Swiss mice were treated orally with ZDV 50 mg/kg/day or distilled water (control), from day eighth of gestation, through delivery and continued for first ten days of lactation. The F1 generation litters were raised and mated to produce F2 generation mice. An interesting phenotype of "healthy" and "sick" was noted in F2 generation but not in the F1 generation. In F2 generation 35% died on different postnatal day during 120 days of follow up period. Chromosomal study from bone marrow of F1 and F2 showed various chromosomal aberrations. Lipodystrophy and hepatotoxicity was observed in "sick" mice. The study generated a hypothesis of recessive mutation and concludes that Zidovudine is a transplacental genotoxic agent. The result of present study therefore suggests the need to study the effect of zidovudine in human subjects for a longer period of time to rule out similar genotoxic effect.
机译：齐多夫定（3'-Azido-2'，3'-二脱氧胸苷，AZT，ZDV）通常被用作抗逆转录病毒疗法的组成部分之一，以防止HIV感染从母体传播到儿童。如先前有关人体，动物和体外实验的研究报道，在怀孕期间服用该药物会产生多种毒性。本研究试图探索母体在怀孕期间最初通过分娩和哺乳接触齐多夫定后在F1和F2代小鼠中产生齐多夫定的致畸作用。实际上，F1代会在胚胎发育和婴儿阶段得到接触。从怀孕的第八天开始，一直到怀孕的瑞士小鼠，口服ZDV 50 mg / kg /天或蒸馏水（对照组），直至分娩，并继续哺乳前十天。饲养F1代垫料并交配以产生F2代小鼠。在F2代中注意到了一个有趣的“健康”和“病态”表型，但在F1代中却没有。在F2代中，有35％的婴儿在随访的120天内于出生后的不同日期死亡。 F1和F2骨髓的染色体研究显示了各种染色体畸变。在“病”的小鼠中观察到了脂肪营养不良和肝毒性。该研究提出了隐性突变的假说，并得出结论认为齐多夫定是一种经胎盘遗传毒性剂。因此，本研究的结果表明需要长期研究齐多夫定在人类受试者中的作用，以排除类似的遗传毒性作用。

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