Tumor-augmenting effects of gestational arsenic exposure on F1 and F2 in mice.
Tumor-augmenting effects of gestational arsenic exposure on F1 and F2 in mice.
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DOI：
10.1186/s41021-016-0069-1
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Takumi S
中科院分区：
文献类型：
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作者：
Nohara K;Suzuki T;Okamura K;Matsushita J;Takumi S
生命早期接触环境中的化学品的后果正在引起人们的关注。长期暴露于天然存在的无机砷已知会导致各种不良健康影响，包括人类癌症。另一方面，M. Waalkes的研究小组报告称，仅在妊娠第8天至第18天，妊娠F0代雌性小鼠的砷暴露增加了C3 H小鼠的F1（砷-F1）雄性小鼠的肝肿瘤，这些雄性小鼠在以后的生活中往往会发生自发性肝肿瘤。由于这种小鼠模型阐明了砷暴露的新的未确定的后果，我们希望进一步研究背景机制。在相同的实验模型中，我们确定了各种因素，妊娠期砷暴露的影响，包括表观遗传和遗传变化，作为亚砷酸盐-F1男性迟发性肝肿瘤增强的多个步骤的可能成分。此外，我们的研究发现，亚砷酸盐-F1雄性所生的F2雄性比对照F2雄性发生肝肿瘤的比率显著更高。结果表明，肿瘤增强效应是遗传的亚砷酸盐-F2男性通过精子的亚砷酸盐-F1。本文就妊娠期砷暴露对F1和F2代小鼠的影响进行了综述，以探讨妊娠期砷暴露生物学效应的新方面。
The consequences of early-life exposure to chemicals in the environment are emerging concerns. Chronic exposure to naturally occurring inorganic arsenic has been known to cause various adverse health effects, including cancers, in humans. On the other hand, animal studies by Dr. M. Waalkes’ group reported that arsenite exposure of pregnant F0 females, only from gestational day 8 to 18, increased hepatic tumors in the F1 (arsenite-F1) males of C3H mice, whose males tend to develop spontaneous hepatic tumors later in life. Since this mice model illuminated novel unidentified consequences of arsenic exposure, we wished to further investigate the background mechanisms. In the same experimental model, we identified a variety of factors that were affected by gestational arsenic exposure, including epigenetic and genetic changes, as possible constituents of multiple steps of late-onset hepatic tumor augmentation in arsenite-F1 males. Furthermore, our study discovered that the F2 males born to arsenite-F1 males developed hepatic tumors at a significantly higher rate than the control F2 males. The results imply that the tumor augmenting effect is inherited by arsenite-F2 males through the sperm of arsenite-F1. In this article, we summarized our studies on the consequences of gestational arsenite exposure in F1 and F2 mice to discuss novel aspects of biological effects of gestational arsenic exposure.