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

重粒子線照射によるヒト正常線維芽細胞の分化の促進

浜田 信行*; 原 孝光*; 舟山 知夫; 坂下 哲哉; 小林 泰彦

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

重粒子線を照射したヒト正常線維芽細胞の生存子孫細胞において、最初に与えられた線量とそのLET値(線エネルギー付与)に依存してコロニー形成能が遅延的に低下することを、これまでにわれわれは明らかにしてきた。今回、照射によって線量・線質依存的に引き起こされた分化の進行の結果、分裂能が低下した細胞が生存子孫細胞の中に誘発されることが、このような放射線誘発遺伝的不安定性の機序である可能性を示した。

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.