Zebrafish as an In Vivo Model to Assess Epigenetic Effects of Ionizing Radiation

Kong, Eva Yi; Cheng, Shuk Han; Yu, K.N.

doi:10.3390/ijms17122108

Cited by 12 publications

(12 citation statements)

References 255 publications

(317 reference statements)

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“…The zebrafish, with a 70% genetic similarity to humans [23] has become a widely used model organism in radiation studies [7, 24, 25] and environmental epigenetics [26]. The early embryonic development is well described [27] and the early gastrula stage embryo at 50% epiboly (5.5 hpf) produces epigenetic signals with a high signal to background ratio, due to its mainly undifferentiated cell population [28].…”

Section: Introductionmentioning

confidence: 99%

Gamma radiation induces locus specific changes to histone modification enrichment in zebrafish and Atlantic salmon

et al. 2019

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Ionizing radiation is a recognized genotoxic agent, however, little is known about the role of the functional form of DNA in these processes. Post translational modifications on histone proteins control the organization of chromatin and hence control transcriptional responses that ultimately affect the phenotype. The purpose of this study was to investigate effects on chromatin caused by ionizing radiation in fish. Direct exposure of zebrafish (Danio rerio) embryos to gamma radiation (10.9 mGy/h for 3h) induced hyper-enrichment of H3K4me3 at the genes hnf4a , gmnn and vegfab . A similar relative hyper-enrichment was seen at the hnf4a loci of irradiated Atlantic salmon (Salmo salar) embryos (30 mGy/h for 10 days). At the selected genes in ovaries of adult zebrafish irradiated during gametogenesis (8.7 and 53 mGy/h for 27 days), a reduced enrichment of H3K4me3 was observed, which was correlated with reduced levels of histone H3 was observed. F1 embryos of the exposed parents showed hyper-methylation of H3K4me3, H3K9me3 and H3K27me3 on the same three loci, while these differences were almost negligible in F2 embryos. Our results from three selected loci suggest that ionizing radiation can affect chromatin structure and organization, and that these changes can be detected in F1 offspring, but not in subsequent generations.

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Section: Introductionmentioning

confidence: 99%

Gamma radiation induces locus specific changes to histone modification enrichment in zebrafish and Atlantic salmon

et al. 2019

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“…Still, the DNA methylation pathways as well as the tissue specific levels of hydroxymethylcytosine (hmC), an intermediate in the demethylation mechanism, are conserved 33 , 38 . Several studies have successfully employed zebrafish for DNA methylation studies following xenobiotic exposures 15 – 17 , 39 – 45 , however information of ionizing radiation induced epigenetic changes in zebrafish is scarce 46 .…”

Section: Introductionmentioning

confidence: 99%

Ionizing radiation induces transgenerational effects of DNA methylation in zebrafish

Kamstra

Hurem

Martín

et al. 2018

Sci Rep

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Ionizing radiation is known to cause DNA damage, yet the mechanisms underlying potential transgenerational effects of exposure have been scarcely studied. Previously, we observed effects in offspring of zebrafish exposed to gamma radiation during gametogenesis. Here, we hypothesize that these effects are accompanied by changes of DNA methylation possibly inherited by subsequent generations. We assessed DNA methylation in F1 embryos (5.5 hours post fertilization) with whole genome bisulfite sequencing following parental exposure to 8.7 mGy/h for 27 days and found 5658 differentially methylated regions (DMRs). DMRs were predominantly located at known regulatory regions, such as gene promoters and enhancers. Pathway analysis indicated the involvement of DMRs related to similar pathways found with gene expression analysis, such as development, apoptosis and cancers, which could be linked to previous observed developmental defects and genomic instability in the offspring. Follow up of 19 F1 DMRs in F2 and F3 embryos revealed persistent effects up to the F3 generation at 5 regions. These results indicate that ionizing radiation related effects in offspring can be linked to DNA methylation changes that partly can persist over generations. Monitoring DNA methylation could serve as a biomarker to provide an indication of ancestral exposures to ionizing radiation.

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“…Ionizing radiation-induced cell damage can result in a variety of deleterious effects during the lifetime of an organism, and as germ cell damage has been found to be transmissible and inherited by future generations, such damage can also result in more long-term population effects (Kong et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Gamma irradiation during gametogenesis in young adult zebrafish causes persistent genotoxicity and adverse reproductive effects

Hurem

Gomes

Brede

et al. 2018

Ecotoxicology and Environmental Safety

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The biological effects of gamma radiation may exert damage beyond that of the individual through its deleterious effects on reproductive function. Impaired reproductive performance can result in reduced population size over consecutive generations. In a continued effort to investigate reproductive and heritable effects of ionizing radiation, we recently demonstrated adverse effects and genomic instability in progeny of parents exposed to gamma radiation. In the present study, genotoxicity and effects on the reproduction following subchronic exposure during a gametogenesis cycle to Co gamma radiation (27 days, 8.7 and 53 mGy/h, total doses 5.2 and 31 Gy) were investigated in the adult wild-type zebrafish (Danio rerio). A significant reduction in embryo production was observed one month after exposure in the 53 mGy/h exposure group compared to control and 8.7 mGy/h. One year later, embryo production was significantly lower in the 53 mGy/h group compared only to control, with observed sterility, accompanied by a regression of reproductive organs in 100% of the fish 1.5 years after exposure. Histopathological examinations revealed no significant changes in the testis in the 8.7 mGy/h group, while in 62.5% of females exposed to this dose rate the oogenesis was found to be only at the early previtellogenic stage. The DNA damage determined in whole blood, 1.5 years after irradiation, using a high throughput Comet assay, was significantly higher in the exposed groups (1.2 and 3-fold increase in 8.7 and 53 mGy/h females respectively; 3-fold and 2-fold increase in 8.7 and 53 mGy/h males respectively) compared to controls. A significantly higher number of micronuclei (4-5%) was found in erythrocytes of both the 8.7 and 53 mGy/h fish compared to controls. This study shows that gamma radiation at a dose rate of ≥ 8.7 mGy/h during gametogenesis causes adverse reproductive effects and persistent genotoxicity (DNA damage and increased micronuclei) in adult zebrafish.

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Zebrafish as an In Vivo Model to Assess Epigenetic Effects of Ionizing Radiation

Cited by 12 publications

References 255 publications

Gamma radiation induces locus specific changes to histone modification enrichment in zebrafish and Atlantic salmon

Gamma radiation induces locus specific changes to histone modification enrichment in zebrafish and Atlantic salmon

Ionizing radiation induces transgenerational effects of DNA methylation in zebrafish

Gamma irradiation during gametogenesis in young adult zebrafish causes persistent genotoxicity and adverse reproductive effects

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