Radiation-induced untargeted germline mutations in Japanese medaka

Tsyusko, Olga V.; Yi, Yang; Coughlin, Daniel P.; Main, Dorrie; Podolsky, Robert H.; Hinton, Thomas G.; Glenn, Travis C.

doi:10.1016/j.cbpc.2006.08.010

Cited by 17 publications

(11 citation statements)

References 58 publications

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“…Nevertheless, we cannot exclude the presence in embryos of other DNA damage (e.g., mutations), which potentially could have an impact on the reproduction success or be transmitted to other generations. This was observed in medaka for chronic exposure [26], where DNA mutations were observed in exposed medaka and mutations were transmitted to offspring from exposed parents.…”

Section: Discussionmentioning

confidence: 79%

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Genotoxicity of acute and chronic gamma-irradiation on zebrafish cells and consequences for embryo development

Pereira

Bourrachot

Cavalié

et al. 2011

Environmental Toxicology and Chemistry

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The effects of radiation on biological systems have been studied for many years, and it is now accepted that direct damage to DNA from radiation is the triggering event leading to biological effects. In the present study, DNA damage induced by acute or chronic irradiation was compared at the cellular (zebrafish [Danio rerio] cell line ZF4) and developmental (embryo) levels. Zebrafish ZF4 cells and embryos (at 3 h postfertilization) were exposed within ranges of acute doses (0.3-2 Gy/d) or chronic dose rates (0.1-0.75 Gy/d). DNA damage was assessed by immunodetection of γ-H2AX and DNA-PK (DNA double-strand breaks) and the alkaline comet assay (DNA single-strand breaks). Zebrafish embryo development and DNA damage were examined after 120 h. At low doses, chronic irradiation induced more residual DNA damage than acute irradiation, but embryo development was normal. From 0.3 Gy, a hyper-radiosensitivity phenomenon compared to other species was shown for acute exposure with an increase of DNA damage, an impairment of hatching success, and larvae abnormalities. These results suggest a dose-dependent correlation between unrepaired DNA damage and abnormalities in embryo development, supporting the use of DNA repair proteins as predictive biomarkers of ionizing radiation exposure. This could have important implications for environmental protection.

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Section: Discussionmentioning

confidence: 79%

“…For larvae of the same species exposed for 24 h, genotoxic effects were also demonstrated from 29 mGy/d using the comet assay [25]. Radiation-induced untargeted germline mutations were also observed in the medaka for chronic exposure (dose rate of 68 mGy/d for 45-153 d) [26].…”

Section: Introductionmentioning

confidence: 95%

Genotoxicity of acute and chronic gamma-irradiation on zebrafish cells and consequences for embryo development

Pereira

Bourrachot

Cavalié

et al. 2011

Environmental Toxicology and Chemistry

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“…Direct identification of de novo germline mutations at microsatellite loci has already been applied in different species (e.g. [30,31]), including humans [32,33] and mice [34], through family pedigree analysis. One of the most powerful microsatellite studies to date applied a pedigree approach in 85,289 individuals at 2477 microsatellites to demonstrate older males transmit more mutations to their offspring, confirming that paternal age is a modulating factor in germline mutation rates [33].…”

Section: Introductionmentioning

confidence: 99%

Single-molecule PCR analysis of an unstable microsatellite for detecting mutations in sperm of mice exposed to chemical mutagens

Beal

Rowan-Carroll

Campbell

et al. 2015

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Single-molecule PCR (SM-PCR) analysis of long and repetitive DNA sequences, known as expanded simple tandem repeats (ESTRs), has been the most efficient method for studying germline mutation induction in endogenous sequences to date. However, the long length of these sequences makes mutation detection imprecise and laborious, and they have been characterized only in mice. Here, we explore the use of unstable microsatellite sequences that can be typed with high precision by capillary electrophoresis as alternative loci for detecting germline mutations. We screened 24 microsatellite loci across inbred mouse strains and identified Mm2.2.1 as the most polymorphic microsatellite locus. We then optimized SM-PCR of Mm2.2.1 to detect mutations in sperm. SM-PCR analysis of sperm from untreated B6C3F1 and Muta(™)Mouse samples revealed mutation frequencies that are consistent with rates derived from family pedigree analysis (∼ 5 × 10(-3)). To determine whether this locus can be used to detect chemically induced germline mutations, Muta(™)Mouse males were exposed by oral gavage to a single dose of 100mg/kg of N-ethyl-N-nitrosourea (ENU) or to 100mg/kg of benzo(a)pyrene (BaP) for 28 days alongside vehicle treated controls. Sperm were collected 10 weeks post-ENU exposure to sample sperm exposed as spermatogonial stem cells and 6 weeks post-BaP exposure to sample sperm that were dividing spermatogonia when the exposure was terminated. Both treatments resulted in a significant (approximately 2-fold) increase in mutation frequency in sperm compared to the control animals. The work establishes the utility of this microsatellite for studying mutation induction in the germ cells of mice. Because microsatellites are found in virtually every species, this approach holds promise for other organisms, including humans.

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“…It is well known that the instability of microsatellites in genome is one of the main trans-generational effects of irradiation 14) . We first screened the genomic database of an inbred medaka strain, Hd-rR, and found more than 10,000 microsatellites in medaka chromosome 9, which would be instable after gamma ray irradiation and selected 15 microsatellites for High-Resolution Melting analysis.…”

Section: Detection Of Genomic Mutation In Micro Satellites By High-rementioning

confidence: 99%

Long-Term Rearing of Medaka Aboard ISS to Clarify the Trans-Generation Effects in Vertebrates Induced by Cosmic Ray Irradiation

Oda

Urushihara

Higa

et al. 2010

AEROSPACE TECHNOLOGY JAPAN

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The effect of cosmic ray irradiation on astronaut health is a major problem to be addressed in the near future, however, it is not clear whether or not long-term irradiation of cosmic ray has trans-generation effects on astronauts. JAXA is developing an AQuatic Habitat system (AQH) that will enable us to keep more than 10 medaka adult fishes for three months on the ISS and we are going to investigate the effects of long-term cosmic ray irradiation on the genomes of vertebrate male germ cells using medaka. Transgenic (TG) medaka males that produce three-color fluorescent sperm are being produced. Cosmic-ray irradiation would induce deletion type DNA lesions and a sperm would lose fluorescence if the deletion occurs in the transgenes in the sperm genome. Because a male produces more than 100 million sperm, we can expect to investigate more than 300 million locus in germ cell genomes per one male fish and will be able to clarify whether long-term cosmic-ray irradiation aboard the ISS would induce serious effects on the vertebrate germ genomes or not and also whether micro gravity on the ISS would enhance mutation in vertebrate germ genomes. The first flight of the TG medaka fishes to the ISS will be in 2012 and will bring us the first data of the effects of long-term cosmic-ray irradiation on vertebrate germ genomes.

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Radiation-induced untargeted germline mutations in Japanese medaka

Cited by 17 publications

References 58 publications

Genotoxicity of acute and chronic gamma-irradiation on zebrafish cells and consequences for embryo development

Genotoxicity of acute and chronic gamma-irradiation on zebrafish cells and consequences for embryo development

Single-molecule PCR analysis of an unstable microsatellite for detecting mutations in sperm of mice exposed to chemical mutagens

Long-Term Rearing of Medaka Aboard ISS to Clarify the Trans-Generation Effects in Vertebrates Induced by Cosmic Ray Irradiation

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