Centre for Radiation Protection Research, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Centre for Radiation Protection Research, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden; University of Caen Normandy, Cimap-Aria, Ganil, and Advanced Resource Center for HADrontherapy in Europe (ARCHADE), Caen, France.
Mutat Res Genet Toxicol Environ Mutagen. 2022 Sep;881:503523. doi: 10.1016/j.mrgentox.2022.503523. Epub 2022 Jul 2.
Ionizing radiation (IR) kills cells mainly through induction of DNA damages and the surviving cells may suffer from mutations. Transgenerational effects of IR are well documented, but the exact mechanisms underlying them are less well understood; they include induction of mutations in germ cells and epigenetic inheritance. Previously, effects in the offspring of mice and zebrafish exposed to IR have been reported. A few studies also showed indications of transgenerational effects of radiation in humans, particularly in nuclear power workers. In the present project, short- and long-term effects of low-dose-rate (LDR; 50 and 97 mGy/h) and high-dose-rate (HDR; 23.4, 47.1 and 495 Gy/h) IR in Drosophila embryos were investigated. The embryos were irradiated at different doses and dose rates and radiosensitivity at different developmental stages was investigated. Also, the survival of larvae, pupae and adults developed from embryos irradiated at an early stage (30 min after egg laying) were studied. The larval crawling and pupation height assays were applied to investigate radiation effects on larval locomotion and pupation behavior, respectively. In parallel, the offspring from 3 Gy irradiated early-stage embryos were followed up to 12 generations and abnormal phenotypes were studied. Acute exposure of embryos at different stages of development showed that the early stage embryo is the most sensitive. The effects on larval locomotion showed no significant differences between the dose rates but a significant decrease of locomotion activity above 7 Gy was observed. The results indicate that embryos exposed to the low dose rates have shorter eclosion times. At the same cumulative dose (1 up to 7 Gy), HDR is more embryotoxic than LDR. We also found a radiation-induced depigmentation on males (A5 segment of the dorsal abdomen, A5pig) that can be transmitted up to 12 generations. The phenomenon does not follow the classical Mendelian laws of segregation.
电离辐射（IR）主要通过诱导 DNA 损伤来杀死细胞，而存活的细胞可能会发生突变。IR 的跨代效应已有充分记录，但对其确切机制的了解较少；它们包括生殖细胞突变的诱导和表观遗传遗传。以前，已经报道了暴露于 IR 的小鼠和斑马鱼后代的影响。一些研究还表明，人类存在辐射的跨代效应，特别是在核电工人中。在本项目中，研究了低剂量率（LDR；50 和 97 mGy/h）和高剂量率（HDR；23.4、47.1 和 495 Gy/h）IR 对果蝇胚胎的短期和长期影响。胚胎在不同剂量和剂量率下进行照射，并研究了不同发育阶段的放射敏感性。此外，还研究了从早期（产卵后 30 分钟）照射的胚胎发育而成的幼虫、蛹和成虫的存活率。幼虫爬行和蛹化高度测定法分别用于研究辐射对幼虫运动和蛹化行为的影响。同时，对经 3Gy 早期胚胎照射的后代进行了 12 代的随访，并研究了异常表型。对不同发育阶段胚胎的急性暴露表明，早期胚胎最敏感。对幼虫运动的影响表明，剂量率之间没有显著差异，但在 7Gy 以上观察到运动活性显著下降。结果表明，暴露于低剂量率的胚胎出芽时间较短。在相同的累积剂量（1 至 7Gy）下，HDR 比 LDR 更具胚胎毒性。我们还发现雄性（背部腹部 A5 节，A5pig）的辐射诱导退色，可传至 12 代。这种现象不符合经典的孟德尔分离定律。
