Host: The Japan Radiation Research Society
Radioadaptive response is a biodefensive response observed in a variety of mammalian cells and animals where exposure to low dose radiation induces resistance against the subsequent high dose radiation. Elucidation of its mechanisms is important for risk estimation of low dose radiation because the radioadaptive response implies that low dose radiation affects cells/individuals in a different manner from high dose radiation. In the present study, we explored molecular mechanisms of the radioadaptive response in human lymphoblastoid cells AHH-1 in terms of mutation at the HPRT gene locus. First we observed that preexposure to the priming dose in the range from 0.02 Gy to 0.2 Gy significantly reduced mutation frequency at HPRT gene locus after irradiation with 3 Gy of X rays. As no significant adaptive response was observed with the priming dose of 0.005 Gy, it was indicated that the lower limit of the priming dose to induce radioadaptive response may be between 0.005 Gy and 0.02 Gy. Second, we examined the effect of 3-aminobenzamide (3AB), an inhibitor of poly(ADP-ribose)polymerase1, which has been reported to inhibit the radioadaptive response in terms of chromosome aberration. However we could observe significant radioadaptive responses in terms of mutation in the presence of 3AB. These findings suggested that molecular mechanisms for the radioadaptive response in terms of mutation may be different from that for radioadaptive responses in terms of chromosomal aberration. Finally, by performing a comprehensive analysis of alterations in gene expression using HiCEP, we could identify 17 genes whose expressions were significantly altered 6h after irradiation with 0.02 Gy. We also found 17 and 20 genes, the expression of which was different with or without priming irradiation 3 and 18 hrs., respectively after challenging irradiation of 3 Gy. By analyzing the gene function, we indicated that expression of genes involved in intracellular signaling and redox-regulation is correlatively altered with radioadaptive responses.
