辐射诱导线虫X染色体主动失活的特性和调控机制研究

染色体畸变分析是辐射生物剂量估算的金标准方法，但畸变的机理仍不很清楚。按照传统的辐射生物学理论，辐射诱导染色体畸变是一个随机、被动的过程，即辐射导致染色体发生断裂/不稳定，然后联接不当导致畸变发生。模式生物线虫有雌雄同体（XX）和雄虫（只有一条X性染色体，XO）两种明确的性别，然而，我们在线虫辐射实验中注意到一个有趣的现象：辐射能诱导部分雌雄同体线虫（XX）转变为雄虫发育表型。进一步分析发现，在该过程中辐射诱导X染色体失活并不是完全随机、被动的，说明生物在染色体层面可能存在对辐射暴露的主动应对机制，为探究其特性和机理，本项目拟开展以下研究：1）辐射暴露线虫X染色体的失活方式；2）线虫X同源染色体的辐射敏感性差异；3）线虫X染色体失活的辐射诱导模式；4）辐射诱导线虫X染色体失活的调控机制。上述研究旨在为这一新的辐射效应模式提供充分的实验证据和机制解析，进一步完善辐射健康风险评估的理论基础。

The analysis of chromosome aberration (CA) is a gold-standard for assessing biological dosage of ionizing radiation (IR), although the underlying mechanisms are not completely clear. According to the traditional theory of radiobiology, IR-induced chromosome aberration is a random and passive process, i.e., IR causes chromosome breakages or instability, and CA occurs when they are not correctly repaired. The model organism Caenorhabditis elegans (C. elegans) has two distinct genders, hermaphrodites (XX) and males (XO). However, we found an interesting phenomenon that IR can transform hermaphrodites into males, in which hermaphrodites voluntarily inactivate an X chromosome in its somatic cells. The results show that at the level of X-chromosome C. elegans might harbor an active mechanism in response to IR. To address this, we firstly investigate the inactivating pattern of X-chromosome when exposed to IR; and then the differences in radio-sensitivity between two homologous X chromosomes. Next, the role of systemic response/IR-induced bystander effects in the inactivation of X-chromosomes will be explained. Finally, we will also address the regulation mechanisms underlying IR-induced inactivation of X-chromosome. Aims of this project are to present robust experimental evidence for the novel radiobiological effect, and lay further theoretical foundations for the assessment of IR healthy risk.