Proton and alpha radiation-induced mutational profiles in human cells.

Proton and alpha radiation-induced mutational profiles in human cells.
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DOI:
10.1038/s41598-023-36845-3
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发表时间:
2023-06-16
期刊:
影响因子:
4.6
通讯作者:
Supek, Fran
Supek, Fran
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Delhomme, Tiffany M.;Munteanu, Maia;Buonanno, Manuela;Grilj, Veljko;Biayna, Josep;Supek, Fran

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电离辐射已知是DNA损伤和致突变的,然而,对于人类细胞暴露于不同类型的辐射导致的突变足迹知之甚少。我们感兴趣的是粒子辐射暴露对各种人类细胞类型基因组的诱变效应,以衡量银河宇宙辐射和某些类型肿瘤放射治疗的遗传毒性风险。为此,我们将来自人类血液、乳腺和肺的培养细胞系暴露于足以显著影响细胞活力的剂量的分级质子和α粒子(氦核)束。全基因组测序显示,在质子和α暴露后,突变率总体上没有显著增加。然而,突变谱和分布有适度的变化,例如聚集突变和某些类型的插入缺失和结构变异的增加。粒子束的致突变效应谱可以是细胞类型和/或遗传背景特异性的。总的来说,反复暴露于质子和α辐射对培养中的人类细胞的突变影响似乎很微妙,但需要进一步的工作来了解长期暴露对各种人体组织的影响。
Ionizing radiation is known to be DNA damaging and mutagenic, however less is known about which mutational footprints result from exposures of human cells to different types of radiation. We were interested in the mutagenic effects of particle radiation exposures on genomes of various human cell types, in order to gauge the genotoxic risks of galactic cosmic radiation, and of certain types of tumor radiotherapy. To this end, we exposed cultured cell lines from the human blood, breast and lung to fractionated proton and alpha particle (helium nuclei) beams at doses sufficient to considerably affect cell viability. Whole-genome sequencing revealed that mutation rates were not overall markedly increased upon proton and alpha exposures. However, there were modest changes in mutation spectra and distributions, such as the increases in clustered mutations and of certain types of indels and structural variants. The spectrum of mutagenic effects of particle beams may be cell-type and/or genetic background specific. Overall, the mutational effects of repeated exposures to proton and alpha radiation on human cells in culture appear subtle, however further work is warranted to understand effects of long-term exposures on various human tissues.
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