Energetic heavy ions accelerate differentiation in the descendants of irradiated normal human diploid fibroblasts

Hamada, Nobuyuki*; Hara, Takamitsu*; Funayama, Tomoo; Sakashita, Tetsuya; Kobayashi, Yasuhiko

Dependence of ionizing radiation-induced genomic instability on the linear energy transfer (LET) of the radiation is incompletely characterized; however, our previous work has shown that delayed reductions in clonogenicity can be most pronounced at LET of 108 keV/m. To gain insight into potential cellular mechanisms involved in LET-dependent delayed loss of clonogenicity, we investigated morphological changes in colonies arising from normal human diploid fibroblasts exposed to -rays or energetic carbon ions (108 keV/m). Exposure of confluent cultures to carbon ions was 4-fold more effective at inactivating cellular clonogenic potential and produced more abortive colonies containing reduced number of cells per colony than -rays. Second, colonies were assessed for clonal morphotypic heterogeneity. The yield of differentiated cells was elevated in a dose- and LET-dependent fashion in clonogenic colonies, whereas differentiated cells predominated to a comparable extent irrespective of radiation type or dose in abortive colonies.