Inverse dose protraction effects of low-LET radiation; Evidence and significance

Hamada, Nobuyuki*; Matsuya, Yusuke  ; Zablotska, L. B.*; Little, M. P.*

Biological effects of ionizing radiation vary not merely with total dose but also with temporal dose distribution. While sparing dose protraction effects where dose protraction reduces effects of radiation have widely been accepted and generally assumed in radiation protection, inverse dose protraction effects (IDPEs) where dose protraction enhances radiation effects have not been well recognized, nor comprehensively reviewed. Here, we review the current knowledge on IDPEs of low LET radiation. Since 1952, 136 biology, epidemiology or clinical papers have heretofore reported IDPEs following low-LET irradiation (i.e., photons, -rays, electrons, protons or helium ions) using cell-free macromolecules (DNA, proteins, or lipids), cultured mammalian cells, insects, animals, and human. In contrast to a growing body of phenomenological evidence for manifestations of IDPEs, there is limited knowledge on mechanistic underpinnings. This review will contribute to ongoing research into the mechanism and to the discussion of the implications of the scientific evidence for radiation protection.