Radiation-induced untargeted germline mutations in Japanese medaka

O. Tsyusko; Y. Yi; D. Coughlin; D. Main; R. Podolsky; T. G. Hinton; T. C. Glenn

doi:10.1016/j.cbpc.2006.08.010

Radiation-induced untargeted germline mutations in Japanese medaka

O. Tsyusko, Y. Yi, D. Coughlin, D. Main, R. Podolsky, T. G. Hinton, T. C. Glenn

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

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 × 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.

Original language	English
Pages (from-to)	103-110
Number of pages	8
Journal	Comparative Biochemistry and Physiology Part - C: Toxicology and Pharmacology
Volume	145
Issue number	1
DOIs	https://doi.org/10.1016/j.cbpc.2006.08.010
State	Published - Feb 2007

Bibliographical note

Funding Information:
We thank Richard Winn for providing medaka brood stocks, DNA and invaluable advice; Mandy Schable, Cris Hagen, Joe Nairn, Brant Faircloth and participants of the 2003 UGA microsatellite development workshop for assistance in isolating microsatellite loci. This work was partially supported by the Office of Science (BER), U. S. Department of Energy (DOE) Grant No.DE-FG02-05ER64087 and by the DOE through Financial Assistance Award No.DE-FC09-96-SR18546 to the University of Georgia Research Foundation.

Keywords

Fitness
Germline mutations
Japanese medaka
Microsatellites
Oryzias latipes
Radiation
Spermatogonia
Untargeted mutations
Variation

ASJC Scopus subject areas

Biochemistry
Physiology
Toxicology
Cell Biology
Health, Toxicology and Mutagenesis

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10.1016/j.cbpc.2006.08.010

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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 × 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.",

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author = "O. Tsyusko and Y. Yi and D. Coughlin and D. Main and R. Podolsky and Hinton, {T. G.} and Glenn, {T. C.}",

note = "Funding Information: We thank Richard Winn for providing medaka brood stocks, DNA and invaluable advice; Mandy Schable, Cris Hagen, Joe Nairn, Brant Faircloth and participants of the 2003 UGA microsatellite development workshop for assistance in isolating microsatellite loci. This work was partially supported by the Office of Science (BER), U. S. Department of Energy (DOE) Grant No.DE-FG02-05ER64087 and by the DOE through Financial Assistance Award No.DE-FC09-96-SR18546 to the University of Georgia Research Foundation. ",

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AU - Yi, Y.

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AU - Main, D.

AU - Podolsky, R.

AU - Hinton, T. G.

AU - Glenn, T. C.

N1 - Funding Information: We thank Richard Winn for providing medaka brood stocks, DNA and invaluable advice; Mandy Schable, Cris Hagen, Joe Nairn, Brant Faircloth and participants of the 2003 UGA microsatellite development workshop for assistance in isolating microsatellite loci. This work was partially supported by the Office of Science (BER), U. S. Department of Energy (DOE) Grant No.DE-FG02-05ER64087 and by the DOE through Financial Assistance Award No.DE-FC09-96-SR18546 to the University of Georgia Research Foundation.

PY - 2007/2

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N2 - 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 × 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.

AB - 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 × 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.

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Radiation-induced untargeted germline mutations in Japanese medaka

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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