Does perfluorooctane sulfonate (PFOS) act as chemosensitizer in zebrafish embryos?

Earlier studies have shown that perfluorooctane sulfonate (PFOS) increases the toxicity of other chemicals by enhancing their uptake by cells and tissues. The present study aimed at testing whether the underlying mechanism of enhanced uptake of chemicals by zebrafish (Danio rerio) embryos in the presence of PFOS is by interference of this compound with the cellular efflux transporter Abcb4. Modifications of uptake/clearance and toxicity of two Abcb4 substrates, the fluorescent dye rhodamine B (RhB) and vinblastine, by PFOS were evaluated using 24 and 48 h post-fertilization (hpf) embryos. Upon 90 min exposure of 24 hpf embryos to 1 mu M RhB and different PFOS concentrations (3-300 mu M) accumulation of RhB in zebrafish was increased by up to 11.9-fold compared to controls, whereas RhB increases in verapamil treatments were 1.7-fold. Co-administration of PFOS and vinblastine in exposures from 0 to 48 hpf resulted in higher vinblastine-caused mortalities in zebrafish embryos indicating increased uptake of this compound. Interference of PFOS with zebrafish Abcb4 activity was further studied using recombinant protein obtained with the baculovirus expression system. PFOS lead to a concentration dependent decrease of the verapamil-stimulated Abcb4 ATPase activity; at higher PFOS concentrations (250, 500 mu M), also the basal ATPase activity was lowered indicating PFOS to be an Abcb4 inhibitor. In exposures of 48 hpf embryos to a very high RhB concentration (200 mu M), accumulation of RhB in embryo tissue and adsorption to the chorion were increased in the presence of 50 or 100 mu M PFOS. In conclusion, the results indicate that PFOS acts as inhibitor of zebrafish Abcb4; however, the exceptionally large PFOS-caused effect amplitude of RhB accumulation in the 1 mu M RhB experiments and the clear PFOS effects in the experiments with 200 mu M RhB suggest that an additional mechanism appears to be responsible for the potential of PFOS to enhance uptake of Abcb4 substrates. (C) 2015 Elsevier B.V. All rights reserved.