Genotoxic effects of microcystins mediated by nitric oxide and mitochondria

<正>Microcystins are potent toxins,produced naturally by cyanobacteria(blue green algae),and they present significant threats to human and animal health(WHO,1999;Chorus,2001;Carmichael et al.,2001;Falconer,2005;IARC,2010;Ma et al.,2015).These cyclic peptides consist of five common core amino     

Cadmium- and calcium-mediated toxicity in rainbow trout (Oncorhynchus mykiss) in vivo: interactions on fitness and mitochondrial endpoints

Rainbow trout were exposed to sublethal waterborne Cd (5 and 10 μg L⁻¹) and dietary Ca (60 mg g⁻¹), individually and in combination, for 30 d to elucidate the interactive effects and evaluate the toxicological significance of mitochondrial responses to these cations in vivo. Indices of fish condition and mortality were measured and livers, centers of metabolic homeostasis, were harvested to assess mitochondrial function and cation accumulation. All indices of condition assessed (body weight, hepatosomatic index and condition factor) were reduced in all the treatment groups. Mortality occurred in the Cd-exposed groups with dietary Ca partly protecting against and enhancing it in the lower and higher Cd exposure, respectively. State 3 mitochondrial respiration was inhibited by 30%, 35% and 40% in livers of fish exposed to Ca, Cd and Cd + Ca, respectively, suggesting reduced ATP turnover and/or impaired substrate oxidation. While the phosphorylation efficiency was unaffected, state 4 and state 4+ (+ oligomycin) respirations were inhibited by all the exposures. Mitochondrial coupling was reduced and transiently restored denoting partially effective compensatory mechanisms to counteract Cd/Ca toxicity. The respiratory dysfunction was associated with accumulation of both Cd and Ca in the mitochondria. Although fish that survived acute effects of Cd and Ca exposure apparently made adjustments to energy generation such that liver mitochondria functioned more efficiently albeit at reduced capacity, reduced fitness was persistent possibly due to increased demands for maintenance and defense against toxicity. Overall, interactions between Cd and Ca on condition indices and mitochondrial responses were competitive or cooperative depending on exposure concentrations and duration.     

Aging-independent and size-dependent genotoxic response induced by titanium dioxide nanoparticles in mammalian cells

Titanium dioxide nanoparticles(TiO_2 NPs) are subjected to various transformation processes(chemical, physical and biological processes) in the environment, potentially affecting their bioavailability and toxic properties. However, the size variation of TiO_2 NPs during aging process and subsequent effects in mammalian cells are largely unknown. The aim of this study was to illustrate the adverse effects of TiO_2 NPs in different sizes(5, 15 and 100 nm) during aging process on human-hamster hybrid(A_L) cells. There was an aging-time dependent enhancement of average hydrodynamic size in TiO_2 NPs stock suspensions. The cytotoxicity of fresh TiO_2 NPs increased in a size-dependent manner; in contrast, their genotoxicity decreased with the increasing sizes of NPs. No significant toxicity difference was observed in cells exposed to either fresh or 60 day-aged TiO_2 NPs. Both Fresh and aged TiO_2 NPs efficiently induced mitochondrial dysfunction and activated Caspase-3/7 in a size-dependent manner.Using mitochondrial-DNA deficient(ρ~0) ALcells, we further discovered that mitochondrial dysfunction made significant contribution to the size-dependent toxicity induced by TiO_2 NPs during the aging process. Taken together, our data indicated that TiO_2 NPs could significantly induced the cytotoxicity and genotoxicity in an aging time-independent and size-dependent manner, which were triggered by mitochondrial dysfunction. Our study suggested the necessity to include size as an additional parameter for the cautious monitoring of TiO_2 NPs disposal before entering the environment.