A Novel Haploid Cell Culture System for Multi-layered Analysis of Radiation Effects on Human Cells

Ionizing radiation causes various types of DNA damage in mammalian cells, leading to tissue reactions and stochastic effects. Different cultured cell lines have been used to study DNA alterations at the molecular level; however, most previous studies have used diploid cells, making it difficult to accurately analyze structural variations (SVs), such as insertions and deletions (indels), in autosomal chromosomes. Here, we report the development of a unique experimental system using HAP1 cells, a human haploid cell line derived from the chronic myeloid leukemia (CML) cell line KBM-7. To compare their biological properties with normal human diploid fibroblasts (NHDFs), we measured radiation sensitivity, protein expression, and DNA damage response. The results showed that HAP1 cells exhibit properties similar to NHDFs. We also demonstrated their usefulness in next-generation sequencing analysis to identify SVs in autosomes caused by ionizing radiation. Therefore, HAP1 cells serve as an ideal model system for investigating molecular radiation signatures.