title: Radiation-induced untargeted germline mutations in Japanese medaka.
abstract: Radiation has been shown to increase mutation frequencies at tandem repeat loci by indirect interactions of radiation with DNA. We studied germline mutations in chronically exposed Japanese medaka (Oryzias latipes) using microsatellite loci. After screening 26 randomly selected loci among unirradiated parents and their 200 offspring, we selected seven highly mutable loci (0.5-1.0 x 10(-2) mutants per locus per gamete) and two bonus loci for further study. To determine if radiation exposure increases mutation frequencies in these loci, medaka were chronically irradiated from subadults through maturation at relatively low dose rates of 68 mGy/d. Total doses for males and females were 10.4 and 3 Gy, respectively. The mean number of mutations for the offspring of exposed families (0.149+/-0.044) was significantly higher (P=0.018) than for control families (0.080+/-0.028), indicating induction of germline mutations from chronic irradiation. This increase in the microsatellite mutation rate is greater than expected from direct interaction of radiation with DNA, suggesting indirect, untargeted mechanism(s) for mutations. This study identified microsatellite loci with a high mutational background in medaka, variation among loci and families as important variables, and demonstrated the usefulness of this fish model for studying radiation-induced germline mutations.
authors.affiliation: Savannah River Ecology Laboratory, University of Georgia, Aiken, SC 29802, USA. tsyusko@srel.edu
authors.forename: O
authors.initials: O
authors.lastname: Tsyusko
authors.forename: Y
authors.initials: Y
authors.lastname: Yi
authors.forename: D
authors.initials: D
authors.lastname: Coughlin
authors.forename: D
authors.initials: D
authors.lastname: Main
authors.forename: R
authors.initials: R
authors.lastname: Podolsky
authors.forename: T G
authors.initials: TG
authors.lastname: Hinton
authors.forename: T C
authors.initials: TC
authors.lastname: Glenn
mesh_terms: D000483:Alleles; D000818:Animals; D004247:DNA / Q000235:genetics / Q000528:radiation effects; D004259:DNA-Directed DNA Polymerase; D003627:Data Interpretation, Statistical; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005298:Fertility / Q000528:radiation effects; D016678:Genome / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000528:radiation effects*; D009990:Oryzias / Q000235:genetics*; D010063:Ovum / Q000528:radiation effects; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004247:DNA; D004259:DNA-Directed DNA Polymerase