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Genetic and epigenetic changes in clonal descendants of irradiated human fibroblasts [strain 2]

ABSTRACT: To study delayed genetic and epigenetic radiation effects, which may trigger radiation-induced carcinogenesis, we have established single-cell clones from irradiated and non-irradiated primary human fibroblasts. Stable clones were endowed with the same karyotype in all analyzed metaphases after 20 population doublings (PDs), whereas unstable clones displayed mosaics of normal and abnormal karyotypes. To account for differences in radiation sensitivity, all experiments were performed with two different embryonic fibroblast strains. After a single dose of 2 Gray more than half of the irradiated clones exhibited radiation-induced genomic instability (RIGI). Methylation arrays identified several hundred differentially methylated genes and nine enriched pathways associated with in vitro ageing. Methylation changes in 259 genes and the MAP kinase signaling pathway were associated with delayed radiation effects (after 20 PDs). Collectively, our results suggest that both genetic and epigenetic changes occur in the progeny of exposed cells that were not damaged directly by irradiation, likely contributing to radiation-induced carcinogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE112873 | GEO | 2018/04/10

REPOSITORIES: GEO

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Genetic and epigenetic changes in clonal descendants of irradiated human fibroblasts [strain 1]

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