Genomic instability induced in the descendants of normal human fibroblasts surviving heavy-ion irradiation

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

Radiation-induced genomic instability (RIGI) encompasses a variety of delayed effects that arise many generations after the initial insult. To address the LET dependence of the manifestation of RIGI, we here investigated the delayed effects arising in the progeny of normal human diploid fibroblasts surviving exposure to low-LET -rays (0.2 keV/m) or high-LET heavy ions (16.2-1610 keV/m). First, we examined delayed loss of clonogenicity and found that carbon ions (18.3 MeV/amu, 108 keV/m) were most effective at reducing the clonogenic survival both in primary and secondary colonies. Second, morphological changes induced in primary colonies were assessed. It was found that while the yield of differentiated cells was increased in a dose- and LET-dependent fashion, the incidence of giant or multinucleated cells was much less frequent. These results suggest that accelerated differentiation may account for LET-dependent delayed loss of clonogenicity.