title: No threshold for the induction of chromosomal damage at clinically relevant low doses of X rays.
abstract: The recent steep increase in population dose from radiation-based medical diagnostics, such as computed tomography (CT) scans, requires insight into human health risks, especially in terms of cancer development. Since the induction of genetic damage is considered a prominent cause underlying the carcinogenic potential of ionizing radiation, we quantified the induction of micronuclei and loss of heterozygosity events in human cells after exposure to clinically relevant low doses of X rays. A linear dose-response relationship for induction of micronuclei was observed in human fibroblasts with significantly increased frequencies at doses as low as 20 mGy. Strikingly, cells exposed during S-phase displayed the highest induction, whereas non S-phase cells showed no significant induction below 100 mGy. Similarly, the induction of loss of heterozygosity in human lymphoblastoid cells quantified at HLA loci, was linear with dose and reached significance at 50 mGy. Together the findings favor a linear-no-threshold model for genetic damage induced by acute exposure to ionizing radiation. We speculate that the higher radiosensitivity of S-phase cells might relate to the excessive cancer risk observed in highly proliferative tissues in radiation exposed organisms.
authors.affiliation: aDepartment of Toxicogenetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. j.j.w.a.boei@lumc.nl
authors.forename: Jan J W A
authors.initials: JJ
authors.lastname: Boei
authors.forename: Sylvia
authors.initials: S
authors.lastname: Vermeulen
authors.forename: Martina M
authors.initials: MM
authors.lastname: Skubakova
authors.forename: Matty
authors.initials: M
authors.lastname: Meijers
authors.forename: Wil A M
authors.initials: WA
authors.lastname: Loenen
authors.forename: Ron
authors.initials: R
authors.lastname: Wolterbeek
authors.forename: Leon H F
authors.initials: LH
authors.lastname: Mullenders
authors.forename: Harry
authors.initials: H
authors.lastname: Vrieling
authors.forename: Micheline
authors.initials: M
authors.lastname: Giphart-Gassler
mesh_terms: D002455:Cell Division / Q000528:radiation effects; D002478:Cells, Cultured / Q000528:radiation effects / Q000648:ultrastructure; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000528:radiation effects / Q000648:ultrastructure; D005805:Genes, MHC Class I / Q000528:radiation effects; D006801:Humans; D019656:Loss of Heterozygosity; D008214:Lymphocytes / Q000528:radiation effects* / Q000648:ultrastructure; D015162:Micronucleus Tests; D011836:Radiation Tolerance; D011859:Radiography; D015203:Reproducibility of Results; D016196:S Phase / Q000528:radiation effects; D014965:X-Rays / Q000009:adverse effects*