title: Charged-particle mutagenesis II.  Mutagenic effects of high energy charged particles in normal human fibroblasts.
abstract: The biological effects of high LET charged particles are a subject of great concern with regard to the prediction of radiation risk in space. In this report, mutagenic effects of high LET charged particles are quantitatively measured using primary cultures of human skin fibroblasts, and the spectrum of induced mutations are analyzed. The LET of the charged particles ranged from 25 KeV/micrometer to 975 KeV/micrometer with particle energy (on the cells) between 94-603 MeV/u. The X-chromosome linked hypoxanthine guanine phosphoribosyl transferase (hprt) locus was used as the target gene. Exposure to these high LET charged particles resulted in exponential survival curves; whereas, mutation induction was fitted by a linear model. The Relative Biological Effect (RBE) for cell-killing ranged from 3.73 to 1.25, while that for mutant induction ranged from 5.74 to 0.48. Maximum RBE values were obtained at the LET of 150 keV/micrometer. The inactivation cross-section (alpha i) and the action cross-section for mutant induction (alpha m) ranged from 2.2 to 92.0 micrometer2 and 0.09 to 5.56 x 10(-3) micrometer2, respectively. The maximum values were obtained by 56Fe with an LET of 200 keV/micrometer. The mutagenicity (alpha m/alpha i) ranged from 2.05 to 7.99 x 10(-5) with the maximum value at 150 keV/micrometer. Furthermore, molecular analysis of mutants induced by charged particles indicates that higher LET beams are more likely to cause larger deletions in the hprt locus.
authors.affiliation: Life Sciences Division, Los Alamos National Laboratory, NM 87545, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Chen
authors.forename: K
authors.initials: K
authors.lastname: Tsuboi
authors.forename: T
authors.initials: T
authors.lastname: Nguyen
authors.forename: T C
authors.initials: TC
authors.lastname: Yang
mesh_terms: D016923:Cell Death; D002470:Cell Survival / Q000528:radiation effects*; D002478:Cells, Cultured / Q000528:radiation effects*; D003359:Cosmic Radiation; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics* / Q000528:radiation effects; D018499:Linear Energy Transfer; D016296:Mutagenesis / Q000528:radiation effects*; D010315:Particle Accelerators; D012062:Relative Biological Effectiveness; D012867:Skin / Q000166:cytology / Q000528:radiation effects
chemical_list: D007041:Hypoxanthine Phosphoribosyltransferase