Late effects in the progeny of bystander human cells are dependent on radiation quality; The Relevance to cancer risk

Autsavapromporn, N.*; Plante, I.*; Liu, C.*; Konishi, Teruaki*; Usami, Noriko*; Funayama, Tomoo; Azzam, E.*; Murakami, Takeshi*; Suzuki, Masao*

Confluent human skin fibroblasts (NB1RGB) were exposed to various types of microbeam with a different linear energy transfer (LET) at mean absorbed doses 0.4 Gy, wherein 0.036-0.4% of the cells were targeted by IR. Following 20 populations post-irradiation, the cells were harvested and assayed for micronucleus formation, mutation assay and protein oxidation. The progeny of bystander cells exposed to X rays and protons showed the persistence of oxidative stress, and correlate with the increased micronucleus formation and mutant fraction. However, such effects were not observed after irradiation by carbon ions. Interestingly, inhibition of GJIC mitigated the damaging effects in the progeny of bystander cells exposed to protons and carbon ions but not X rays. These data show carbon ions can reduce cancer risk after microbeam irradiation compared with X rays or protons, and GJIC may be a critical mediator in the observed effect.