title: Copper oxide and zinc oxide nanomaterials act as inhibitors of multidrug resistance transport in sea urchin embryos: their role as chemosensitizers.
abstract: The ability of engineered nanomaterials (NMs) to act as inhibitors of ATP-binding cassette (ABC) efflux transporters in embryos of white sea urchin (Lytechinus pictus) was studied. Nanocopper oxide (nano-CuO), nanozinc oxide (nano-ZnO), and their corresponding metal ions (CuSO4 and ZnSO4) were used as target chemicals. The results showed that nano-CuO, nano-ZnO, CuSO4, and ZnSO4, even at relatively low concentrations (0.5 ppm), significantly increased calcein-AM (CAM, an indicator of ABC transporter activity) accumulation in sea urchin embryos at different stages of development. Exposure to nano-CuO, a very low solubility NM, at increasing times after fertilization (>30 min) decreased CAM accumulation, but nano-ZnO (much more soluble NM) did not, indicating that metal ions could cross the hardened fertilization envelope, but not undissolved metal oxide NMs. Moreover, nontoxic levels (0.5 ppm) of nano-CuO and nano-ZnO significantly increased developmental toxicity of vinblastine (an established ABC transporter substrate) and functioned as chemosensitizers. The multidrug resistance associated protein (MRP, one of ABC transporters) inhibitor MK571 significantly increased copper concentrations in embryos, indicating ABC transporters are important in maintaining low intracellular copper levels. We show that low concentrations of nano-CuO and nano-ZnO can make embryos more susceptible to other contaminants, representing a potent amplification of nanomaterial-related developmental toxicity.
authors: †State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210023, P.R. China.|‡Bodega Marine Laboratory, University of California, Davis, Bodega Bay, California 94923, United States.
authors: Bing
authors: B
authors: Wu
authors: ‡Bodega Marine Laboratory, University of California, Davis, Bodega Bay, California 94923, United States.
authors: Cristina
authors: C
authors: Torres-Duarte
authors: ‡Bodega Marine Laboratory, University of California, Davis, Bodega Bay, California 94923, United States.
authors: Bryan J
authors: BJ
authors: Cole
authors: ‡Bodega Marine Laboratory, University of California, Davis, Bodega Bay, California 94923, United States.|§Departments of Environmental Toxicology and Nutrition, University of California, Davis, California 95616, United States.
authors: Gary N
authors: GN
authors: Cherr
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002970:Cleavage Stage, Ovum / Q000187:drug effects; D003300:Copper / Q000378:metabolism / Q000633:toxicity*; D003432:Cross-Linking Reagents / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism*; D005306:Fertilization / Q000187:drug effects; D005452:Fluoresceins / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D049329:Nanostructures / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012617:Sea Urchins / Q000187:drug effects / Q000196:embryology*; D012995:Solubility; D014747:Vinblastine / Q000633:toxicity; D015034:Zinc Oxide / Q000633:toxicity*
chemical_list: D003432:Cross-Linking Reagents; D005452:Fluoresceins; D017382:Reactive Oxygen Species; C085925:calcein AM; D014747:Vinblastine; D003300:Copper; D015034:Zinc Oxide; C000520:cuprous oxide