Whole-genome sequencing–based analysis of low dose rate radiation–induced mutations in normal human fibroblast NB1RGB

Ionising radiation induces various types of DNA damage, which, if not repaired correctly, lead to mutations. Nonetheless, the association between radiation exposure and hereditary effects has not yet been confirmed in humans. In this study, we used WGS to study low dose rate radiation–induced mutations in cultured human cells. Normal human fibroblast NB1RGB cells were seeded as single cells by limiting dilution and grown under irradiation with 137 Cs γ-irradiation of 1 or 20 mGy day -1 for 21 days. The genomic DNA prepared from respective clones or the bulk culture was sequenced using the Illumina NGS platform with paired-end 150-bp reads with reference to the standard human genome assembly GRCh38. By subtracting the calls in the bulk culture and applying several filters, approximately 750–1200 single-nucleotide polymorphisms (SNPs) and 2500 small insertions/deletions (indels) per clone were obtained on average. The number was not substantially different between unirradiated and irradiated cultures. Spectral analysis revealed that the C > A transversion, which is associated with guanine oxidation, was dominant.