Radiation-induced adaptive response. In vitro and in utero studies

Pre-exposure to low dose radiation reduces the biological effects of a subsequent higher challenging dose and the phenomenon is called radiation-induced adaptive response (AR). Described here are author's experimental findings of AR in mice during late embryogenesis and in human lymphoblastoid cells irradiated by high linear energy transfer (LET) radiation. In the former, pregnant ICR mice at the gestation day 11 (E11) were exposed to priming X-irradiation with 0.3 Gy at 0.34 or 4.2 Gy/min where AR had been known to be induced, or with 0.3-1 Gy at 2.5-0.34 Gy/min, the ineffective doses/dose rates for AR. On E12, fetal RNA was subjected to microarray analysis for gene expression levels. In utero, AR specific gene modulations were firstly observed in such genes as for signal transduction, p53, development, etc. In the latter human cell system above, cells of TK6 (p53 +/+), AHH-1 (+/-) and NH32 (p53-knockout) were exposed to priming radiation of either X-ray or heavy ion (0.02 Gy to AHH-1, 0.1 Gy to TK6) and after 6hr, to challenging radiation of different LETs (X-ray, C-ion: 15 and 40 keV/μm and Ne-ion: 150 keV/μm). Mutation was examined with hypoxanthine phosphoribosyltransferase (HPRT) test, and DNA double strand breaks and their repair, with flow cytometry following γ-H2AX phosphorylation kinetics. LET-dependent mutation by challenging heavy ions was observed but its frequency was decreased by pre-exposure in p53+/+ and +/- cells; and neither cell cycle effect nor apoptosis was involved in AR mechanism but DNA repair was suggested involved. Further studies on AR were thought necessary incorporating the factors of bystander effect and genomic instability. (K.T.)