Research of the adaptive response induced by low-dose radiation: where have we been and where should we go?

Adaptive response (AR) induced by low-dose radiation (LDR), originally described by Olivieri et al is the induction of cellular resistance to genotoxic effects caused by subsequently high-dose radiation (HDR). Doses which are effective in inducing AR are called adapting dose or AR dose. So far, AR has been characterized both in vitro with human, rabbit and calf lymphocytes, normal or tumor cell lines, and in vivo with mouse bone marrow cells, splenocytes and germ cells. AR could be expressed in multiple biological endpoints including unscheduled DNA synthesis, micronuclei, chromosome aberrations, gene mutation and cell survival (Figure 1). LDR-induced AR made cells more resistant not only to radiation, but also to hydrogen peroxide (H2O2) and anticancer drugs. Similarly, AR caused by exposure to subtoxic level (or low dose) of non-radiation agents such as H2O2, anticancer drugs and hyperthermia could protect against raditaion-induced damage. AR doses were found to be between 0.05 ± 0.20 Gy for a single exposure to low LET radiation, which is just within the de®nition of LDR by UNSCEAR (0.2 Gy). Within 0.2 Gy AR was negative correlation with AR doses. Range of chronic AR doses is a relative broad. An optimal range of AR doses is required to induce AR (Figure 2), and might vary depending on the exposure dose rate. Mechanisms underlying AR induced by LDR are still unclear, but several hypotheses have been considered (Figure 1). LDR enhances DNA repair ability and antioxidant activity, and produces protective proteins to minimize the indirect damaging effects of subsequent HDR. ± 7 Increase in apoptotic cell death was considered another mechanism for the induction of cytogenetic AR. Although further studies are required to illustrate both phenomenological features and the mechanism of LDR-induced AR, it is important that the biological signi®cance and implication of AR need to be addressed. In this review, therefore, I would like to discuss the following questions.