PMID- 25229974 OWN - NLM STAT- MEDLINE DCOM- 20141214 LR - 20141011 IS - 1938-5404 (Electronic) IS - 0033-7587 (Linking) VI - 182 IP - 4 DP - 2014 Oct TI - Induction of chromosomal aberrations at fluences of less than one HZE particle per cell nucleus. PG - 368-79 LID - 10.1667/RR13721.1 [doi] AB - The assumption of a linear dose response used to describe the biological effects of high-LET radiation is fundamental in radiation protection methodologies. We investigated the dose response for chromosomal aberrations for exposures corresponding to less than one particle traversal per cell nucleus by high-energy charged (HZE) nuclei. Human fibroblast and lymphocyte cells were irradiated with several low doses of <0.1 Gy, and several higher doses of up to 1 Gy with oxygen (77 keV/mum), silicon (99 keV/mum) or Fe (175 keV/mum), Fe (195 keV/mum) or Fe (240 keV/mum) particles. Chromosomal aberrations at first mitosis were scored using fluorescence in situ hybridization (FISH) with chromosome specific paints for chromosomes 1, 2 and 4 and DAPI staining of background chromosomes. Nonlinear regression models were used to evaluate possible linear and nonlinear dose-response models based on these data. Dose responses for simple exchanges for human fibroblasts irradiated under confluent culture conditions were best fit by nonlinear models motivated by a nontargeted effect (NTE). The best fits for dose response data for human lymphocytes irradiated in blood tubes were a linear response model for all particles. Our results suggest that simple exchanges in normal human fibroblasts have an important NTE contribution at low-particle fluence. The current and prior experimental studies provide important evidence against the linear dose response assumption used in radiation protection for HZE particles and other high-LET radiation at the relevant range of low doses. FAU - Hada, Megumi AU - Hada M AD - a Universities Space Research Association, Houston, Texas 77058. FAU - Chappell, Lori J AU - Chappell LJ FAU - Wang, Minli AU - Wang M FAU - George, Kerry A AU - George KA FAU - Cucinotta, Francis A AU - Cucinotta FA LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20140917 PL - United States TA - Radiat Res JT - Radiation research JID - 0401245 SB - IM MH - Cell Nucleus/*genetics/*radiation effects MH - Chromosome Aberrations/*radiation effects MH - Cosmic Radiation/*adverse effects MH - Dose-Response Relationship, Radiation MH - Endpoint Determination MH - Fibroblasts/cytology/radiation effects MH - Humans MH - Linear Energy Transfer EDAT- 2014/09/18 06:00 MHDA- 2014/12/17 06:00 CRDT- 2014/09/18 06:00 PHST- 2014/09/18 06:00 [entrez] PHST- 2014/09/18 06:00 [pubmed] PHST- 2014/12/17 06:00 [medline] AID - 10.1667/RR13721.1 [doi] PST - ppublish SO - Radiat Res. 2014 Oct;182(4):368-79. doi: 10.1667/RR13721.1. Epub 2014 Sep 17.