Differential modification of the C. elegans proteome in response to acute and chronic gamma radiation: link with reproduction decline

Ecosystems are chronically exposed to ionizing radiations. But environmental risk assessment of chronic exposure suffers from a lack of knowledge. Extrapolation of data from acute to chronic exposure is not always relevant, and can lead to uncertainties. In fact, effects could be different between the two irradiation modes, especially regarding reproduction endpoint, which is an ecologically relevant parameter . The free living nematode Caenorhabditis elegans is a particularly appropriate model organism to address this proteomic issues. With its fully sequenced genome and its short life cycle, C. elegans has been successfully used to study acute and chronic irradiation effects and their consequences on germline development and hatching. Results showed that a decrease of the number of progeny associated with a decrease of hatching success occurred from and above 30 Gy of acute irradiation.. In the present study, we decided to refine the understanding of molecular mechanisms of acute and chronic irradiation by a global proteome analysis. To do so, C. elegans were exposed to 3 common cumulated doses between acute and chronic exposure. These 3 doses, lower than the doses for which an effect on the reproduction was shown, were susceptible to allow us to find early and sensitive biomarkers of a reproduction decline. After exposure, global modification of the proteome expression was studied using a label free LC-MS/MS proteomic approach. Our objectives were to test the following hypotheses: (1) whether or not proteome expression varied with the dose, and with the irradiation mode; (2) if proteome expression modification was associated with effects on reproduction, with potential direct implications for ecological risk assessment.

生态系统长期处于电离辐射（ionizing radiations）暴露环境中，但针对慢性辐射暴露的环境风险评估却因相关认知不足而受限。将急性暴露数据外推至慢性暴露场景的做法并非总是合理，且可能引入不确定性。事实上，两种辐照模式下的生物效应可能存在差异，尤其是在繁殖终点这一具有生态学意义的关键参数方面。自由生活线虫秀丽隐杆线虫（Caenorhabditis elegans, C. elegans）是解决此类蛋白质组学（proteomics）研究问题的理想模式生物。该物种拥有已完成全测序的基因组且生命周期较短，已被成功应用于辐照急性与慢性效应及其对生殖系发育、孵化率影响的相关研究。研究结果显示，当急性辐照剂量达到或超过30戈瑞（Gy）时，会出现子代数量减少且孵化成功率下降的现象。本研究旨在通过全蛋白质组分析，进一步阐明急性与慢性辐照的分子作用机制。为此，我们将秀丽隐杆线虫暴露于急性与慢性辐照场景下共3种常见的累积剂量。这3种剂量均低于已被证实会对繁殖产生影响的阈值剂量，有望帮助我们筛选出繁殖能力下降的早期敏感生物标志物。辐照暴露后，我们采用无标记液相色谱-串联质谱（label free LC-MS/MS）蛋白质组学方法，对蛋白质组表达的整体变化进行了分析。本研究的目标为验证以下两项假设：（1）蛋白质组表达是否会随辐照剂量及辐照模式的不同而发生变化；（2）蛋白质组表达的改变是否与繁殖效应相关，以期为环境风险评估提供直接的潜在参考依据。