Combined effects of alpha particles and depleted uranium on Zebrafish ( Danio rerio ) embryos

Abstract

The combined effects of low-dose or high-dose alpha particles and depleted uranium (DU) in Zebrafish (Danio rerio) embryos were studied. Three schemes were examined—(i) [ILUL]: 0.44 mGy alpha-particle dose + 10 µg/l DU exposure, (ii) [IHUH]: 4.4 mGy alpha-particle dose + 100 µg/l DU exposure and (iii) [IHUL]: 4.4 mGy alpha-particle dose + 10 µg/l DU exposure—in which Zebrafish embryos were irradiated with alpha particles at 5 h post fertilization (hpf) and/or exposed to uranium at 5–6 hpf. The results were also compared with our previous work, which studied the effects of [ILUH]: 0.44 mGy alpha-particle dose + 100 µg/l DU exposure. When the Zebrafish embryos developed to 24 hpf, the apoptotic signals in the entire embryos, used as the biological endpoint for this study, were quantified. Our results showed that [ILUL] and [IHUL] led to antagonistic effects, whereas [IHUH] led to an additive effect. The effect found for the previously studied case of [ILUH] was difficult to define because it was synergistic with reference to the 100 µg/l DU exposure, but it was antagonistic with reference to the 0.44 mGy alpha-particle dose. All the findings regarding the four different schemes showed that the combined effects critically depended on the dose response to each individual stressor. We also qualitatively explained these findings in terms of promotion of early death of cells predisposed to spontaneous transformation by alpha particles, interacting with the delay in cell death resulting from various concentrations of DU exposure.

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“…depended on the magnitudes as well as sequences of application of the individual stressors [12][13][14], e.g., a priming low α-particle dose antagonized the effect of a challenging high Cd dose [12], while a priming low Cd dose antagonized the effect of a challenging high α-particle dose [13], and a simultaneous exposure to high doses of α-particles and Cd led to additive and synergistic effect, with the additive effect likely a manifestation of the weakly synergistic effect [14]. On the other hand, the results on combined effects of α-particles and DU [15,16] are summarized in Figure 2 to help readers und Figure 2. Multiple stressor effects from studies on combined effects of α-particles and depleted uranium (DU) on zebrafish (Danio rerio) embryos [15,16].…”

“…As described in Section 1 above, Ng et al examined the multiple stressor effects of α-particles and depleted uranium on zebrafish embryos [15,16], and identified the presence of additive effect, antagonistic effect as well as a "difficult-to-define" multiple stressor effect. The multiple stressor effects were already sophisticated as shown in Figure 2, by taking into account the biphasic hormetic dose-response relationship for both α-particle irradiation and depleted uranium exposure.…”

“…Now that triphasic dose-response relationships have been discovered for both ionizing radiations and phthalates, even more sophisticated dose-response relationships could be anticipated, and attempt to explore the underlying explanations could be even more challenging. In the same research [15,16], the authors stressed the importance of examining the multiple stressor effects from individual stressors at both low and high doses in view of the biphasic characteristics of the dose-response relationships (see Figure 2). With the advent of the triphasic dose-response relationships, it becomes apparent that the multiple stressor effects should be determined from individual stressors at ultra-low, low as well as high doses.…”

“…In reality, multiple stressor effects are not necessarily a simple sum of the effects from individual stressors [10,11], but can be represented by additive, synergistic, antagonistic, or even more complicated relationships. Our group previously performed a series of studies on multiple stressor effects on zebrafish (Danio rerio) embryos using different combinations of individual stressors, including α-particles and cadmium (Cd) [12][13][14], and α-particles and depleted uranium (DU) [15,16]. The results obtained using α-particles and Cd demonstrated that the multiple stressor effects depended on the magnitudes as well as sequences of application of the individual stressors [12][13][14], e.g., a priming low α-particle dose antagonized the effect of a challenging high Cd dose [12], while a priming low Cd dose antagonized the effect of a challenging high α-particle dose [13], and a simultaneous exposure to high doses of α-particles and Cd led to additive and synergistic effect, with the additive effect likely a manifestation of the weakly synergistic effect [14].…”

“…On the other hand, the results on combined effects of α-particles and DU [15,16] are summarized in Figure 2 to help readers und Figure 2. Multiple stressor effects from studies on combined effects of α-particles and depleted uranium (DU) on zebrafish (Danio rerio) embryos [15,16]. Conditions 1 to 4: [IL] and [IH] refer to low and high α-particle doses, respectively; [UL] and [UH] refer to low and high DU exposures, respectively.…”