Nohara Keiko, Suzuki Takehiro, Okamura Kazuyuki, Matsushita Junya, Takumi Shota
Center for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba, 305-8506 Japan.
Graduate School of Pharmaceutical Science, Tokyo University of Science, Noda, 278-8510 Japan.
Genes Environ. 2017 Mar 1;39:3. doi: 10.1186/s41021-016-0069-1. eCollection 2017.
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.
早年接触环境中的化学物质所产生的后果正日益引起人们的关注。长期接触天然存在的无机砷已知会对人类造成各种不良健康影响，包括癌症。另一方面，M. 瓦尔克斯博士团队的动物研究报告称，仅在妊娠第8天至18天对怀孕的F0雌性小鼠进行亚砷酸盐暴露，会增加C3H小鼠F1（亚砷酸盐-F1）雄性后代的肝脏肿瘤，该品系雄性小鼠在生命后期往往会自发发生肝脏肿瘤。由于这个小鼠模型揭示了砷暴露的新的未知后果，我们希望进一步研究其背后的机制。在相同的实验模型中，我们确定了多种受孕期砷暴露影响的因素，包括表观遗传和基因变化，这些因素可能是亚砷酸盐-F1雄性小鼠后期肝脏肿瘤增加多个步骤的组成部分。此外，我们的研究发现，亚砷酸盐-F1雄性小鼠所生的F2雄性后代发生肝脏肿瘤的比率明显高于对照F2雄性小鼠。结果表明，肿瘤增强效应通过亚砷酸盐-F1的精子遗传给亚砷酸盐-F2雄性小鼠。在本文中，我们总结了我们对F1和F2小鼠孕期亚砷酸盐暴露后果的研究，以讨论孕期砷暴露生物效应的新方面。
