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

Abstract

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.

Embryonic ionizing radiation exposure results in expression alterations of genes associated with cardiovascular and neurological development, function, and disease and modified cardiovascular function in zebrafish

“…This initial toxicity assay provided baseline toxicity of IR in our laboratory at the specific doses at the specific developmental time point of exposure for comparison to previous completed studies with the zebrafish model system. Our findings are similar to those reported in the literature for radiation exposure at this developmental time point, while exposure at earlier developmental stages is reported as more toxic (McAleer et al, 2005; Geiger et al, 2006; Pereira et al, 2011). McAleer et al (2005) and Geiger et al (2006) observed that lethal effects of IR were inversely proportional to embryonic age with earlier embryonic stages (e.g., 2–6 hpf) being more sensitive to lethality than later embryonic stages (e.g., 8–24 hpf).…”

“…Previous studies using the zebrafish model system to evaluate ionizing radiation exposure have been used to assess general toxicity (e.g., mortality, hatching rates, gross morphological alterations, DNA damage, and apoptosis) (e.g., Bladen et al, 2007; Choi et al, 2010a,b, 2012a, 2013; Pereira et al, 2011; Sorrells et al, 2012; Yu et al, 2012; Toruno et al, 2014), to screen radiation protectors (McAleer et al, 2005; Geiger et al, 2006), and to assess the long-term effects on liver gene expression (Jaafar et al, 2013). To the best of our knowledge, no work is published on the effect of IR to heart rate using the zebrafish model.…”

Chronic exposure by ingestion of environmentally relevant doses of226Ra leads to transient growth perturbations in fathead minnow (Pimephales promelas, Rafinesque, 1820)

“…Fish as a large class of the vertebrates are one of the most studied groups of animals in toxicology and radiobiology because of their key position in aquatic ecosystems (Real et al 2004, Pereira et al 2011, Smith et al 2011a, Tsyusko et al 2011, Mothersill and Seymour 2012, Olsvik et al 2012. Th ey are considered to be relatively radioresistant (Choppin et al 2002), but close examination of the data suggest that the radioresistance is limited to adult fi sh and that lethality is the endpoint (Whicker and Schultz 1982).…”

“…Th ey are considered to be relatively radioresistant (Choppin et al 2002), but close examination of the data suggest that the radioresistance is limited to adult fi sh and that lethality is the endpoint (Whicker and Schultz 1982). Recent studies using embryos of zebrafi sh, salmonids and earthworms , Yum et al 2010, Hertel-Aas et al 2011a, Pereira et al 2011) suggest a very sensitive response to radiation and other mutagens. Th is means that in the wild, the fi sh could be impacted by exposure to radiation at environmentally relevant levels, with consequent eff ects on aquatic food webs.…”

Proteínas transmembranales de organismos tipo rickettsia (OTR) en animales acuáticos: Factores de adherencia, invasión e infección

“…Además, se encontró evidencia de sub unidades de Ku70 en una amplia diversidad de organismos marinos tanto vertebrados como invertebrados (Kanungo et al 1999, Pereira et al 2011, Rhee et al 2012). …”