Transcriptome-Wide Prediction and Measurement of Combined Effects Induced by Chemical Mixture Exposure in Zebrafish 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) [I L U L ]: 0.44 mGy alpha-particle dose + 10 µg/l DU exposure, (ii) [I H U H ]: 4.4 mGy alpha-particle dose + 100 µg/l DU exposure and (iii) [I H U L ]: 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 [I L U H ]: 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 [I L U L ] and [I H U L ] led to antagonistic effects, whereas [I H U H ] led to an additive effect. The effect found for the previously studied case of [I L U H ] 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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Transgenic (cyp19a1b-GFP) zebrafish embryos as a tool for assessing combined effects of oestrogenic chemicals

Aquatic Toxicology ◽

10.1016/j.aquatox.2013.05.001 ◽

2013 ◽

Vol 138-139 ◽

pp. 88-97 ◽

Cited By ~ 33

Author(s):

Karina Petersen ◽

Eva Fetter ◽

Olivier Kah ◽

François Brion ◽

Stefan Scholz ◽

...

Keyword(s):

Zebrafish Embryos ◽

Combined Effects

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Toxicities of microplastic fibers and granules on the development of zebrafish embryos and their combined effects with cadmium

Chemosphere ◽

10.1016/j.chemosphere.2020.128677 ◽

2020 ◽

pp. 128677

Author(s):

Haodong Cheng ◽

Yifan Feng ◽

Zhenghua Duan ◽

Xinyue Duan ◽

Shuang Zhao ◽

...

Keyword(s):

Zebrafish Embryos ◽

Combined Effects

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Effects of Retinoic Acid and 1,25-Dihydroxyvitamin D3 on IFN-gamma Secretion by Mononuclear Leukocytes from Nulliparous and Postparturient Dairy Cattle

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.70.3.92 ◽

2000 ◽

Vol 70 (3) ◽

pp. 92-101 ◽

Cited By ~ 14

Author(s):

Burim Ametaj ◽

Brian Nonnecke ◽

Ronald Horst ◽

Donald Beitz

Keyword(s):

Retinoic Acid ◽

Dairy Cattle ◽

Dairy Cows ◽

Dairy Cow ◽

Pokeweed Mitogen ◽

Mononuclear Leukocytes ◽

Combined Effects ◽

Ifn Gamma ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D

Individual and combined effects of several isomers of retinoic acid (RA) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on interferon-gamma (IFN-gamma) secretion by blood mononuclear leukocytes (MNL) from nulliparous and postparturient Holstein cattle were evaluated in vitro. In the first experiment, effects on incubation period (24 to 72 hours) and time of supplementation (0 to 32 hours) with all-trans, 9-cis, 13-cis-, and 9,13-dicis-RAs (0 to 100 nM) on IFN-gamma secretion by pokeweed mitogen (PWM)-stimulated (0 and 10 mug/ml) MNL from nulliparous cattle were evaluated. In the second experiment, MNL from postparturient cows (bled at 0, 2, 4, and 16 days postpartum) were stimulated with PWM (0 and 10 mug/ml) in the presence of RA isomers (9-cis- or 9,13-dicis-RA; 0 to 100 nM), 1,25-(OH)2D3 (0 to 100 nM), or with combinations of these metabolites. The results show that individual isomers of RA had no effect on IFN-gamma secretion by PWM-stimulated MNL from nulliparous or postparturient cows. Furthermore 1,25-dihydroxyvitamin D3 inhibited IFN-gamma secretion by MNL from nulliparous and postparturient dairy cows; however, the degree of inhibition was greater when 9-cis- and 9,13-dicis-RA were also present in the cultures. Finally mononuclear leukocytes from postparturient dairy cows produced substantially less IFN-gamma than did MNL from nulliparous cattle. It is concluded that retinoic acids individually did not affect the capacity of leukocytes from dairy cattle to secrete IFN-gamma. This result is in marked contrast to studies in monogastric species indicating that RAs inhibit IFN-gamma secretion by peripheral blood T cells. Inhibition of IFN-gamma secretion by 1,25-(OH)2D3 was potentiated by 9-cis- and 9,13-di-cis-retinoics acids, suggesting that an excess of dietary vitamins A and D may compromise further the naturally immunosuppressed postparturient dairy cow. Additional research is necessary to determine if the combined effects of these metabolites on IFN-gamma secretion represent an increased susceptibility of the dairy cow to infectious diseases during the periparturient period. Lower secretion of IFN-gamma by MNL from postpartutient dairy cows, relative to nulliparous cattle, suggests that recently-calved cows are naturally immunosuppressed.

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