Institute of Biology of Komi Scientific Centre of the Ural Branch of the Russian Academy of Science, Syktyvkar, Russia.
Radiat Environ Biophys. 2020 May;59(2):221-236. doi: 10.1007/s00411-020-00833-2. Epub 2020 Feb 19.
The article is devoted to the study of the role of intracellular mechanisms in the formation of radiation-induced genetic instability and its transgenerational effect in cells of different tissues of the descendants of Drosophila melanogaster mutant strains whose parents were exposed to chronic radiation (0.42 and 3.5 mGy/h). The level of DNA damage (alkali-labile sites (ALS), single-strand (SSB) and double-strand (DSB) breaks) in cells of somatic (nerve ganglia, imaginal discs) and generative (testis) tissues from directly irradiated animals and their unirradiated offspring was evaluated. Confident transgenerational instability (on the level of ALSs and SSBs), observed only in somatic tissues and only at the higher dose rate, is characteristic for mus209 mutant strains defective in excision repair and, less often, for mus205 and mus210 mutant strains. The greatest manifestation of radiation-induced genetic instability was found in evaluating the DSBs. Dysfunction of the genes mus205, mus304, mei-9 and mei-41, which are responsible for postreplicative repair, excision repair, recombination and control of the cell cycle, affects transgenerational changes in the somatic tissues of the offspring of parents irradiated in both low and high dose rates. In germ cells, the key role in maintaining genetic stability under chronic irradiation is played by the non-recombination postreplication repair mus101 gene. We revealed the tissue specificity of the radiation-induced effects, transgenerational transmission and accumulation of DNA damage to descendants of chronically irradiated animals.
本文致力于研究细胞内机制在辐射诱导遗传不稳定性形成及其在黑腹果蝇突变株后代不同组织细胞中的跨代效应中的作用,这些突变株的父母受到慢性辐射(0.42 和 3.5 mGy/h)的照射。评估了直接照射动物及其未照射后代的体细胞(神经节、生殖腺)和生殖细胞(睾丸)组织中 DNA 损伤的水平(碱不稳定部位(ALS)、单链(SSB)和双链(DSB)断裂)。在更高的剂量率下,只有在体细胞组织中才会观察到具有跨代不稳定性(在 ALS 和 SSB 水平上)的情况,这是 mus209 突变株的特征,该突变株在切除修复中存在缺陷,而 mus205 和 mus210 突变株则较少见。在评估 DSB 时,发现了辐射诱导遗传不稳定性的最大表现。负责复制后修复、切除修复、重组和细胞周期控制的基因 mus205、mus304、mei-9 和 mei-41 的功能障碍,会影响父母在低剂量率和高剂量率下照射的后代体细胞的跨代变化。在生殖细胞中,非重组复制后修复的 mus101 基因在维持遗传稳定性方面起着关键作用。我们揭示了慢性照射下组织特异性的辐射诱导效应、跨代传递和 DNA 损伤在后代中的积累。