Jungkon Kim

Endocrine disruption and consequences of chronic exposure to ibuprofen in Japanese medaka (Oryzias latipes) and freshwater cladocerans Daphnia magna and Moina macrocopa

Despite frequent detection of ibuprofen in aquatic environments, the hazards associated with long-term exposure to ibuprofen have seldom been investigated. Ibuprofen is suspected of influencing sex steroid hormones through steroidogenic pathways in both vertebrates and invertebrates. In this study, the effect of ibuprofen on sex hormone balance and the associated mechanisms was investigated in vitro by use of H295R cells. We also conducted chronic toxicity tests using freshwater fish, Oryzias latipes, and two freshwater cladocerans, Daphnia magna and Moina macrocopa, for up to 144 and 21d of exposure, respectively. Ibuprofen exposure increased 17beta-estradiol (E2) production and aromatase activity in H295R cells. Testosterone (T) production decreased in a dose-dependent manner. For D. magna, the 48 h immobilization EC50 was 51.4 mg/L and the 21 d reproduction NOEC was <1.23 mg/L; for M. macrocopa, the 48 h immobilization EC50 was 72.6 mg/L and the 7d reproduction NOEC was 25mg/L. For O. latipes, 120 d survival NOEC was 0.0001 mg/L. In addition, ibuprofen affected several endpoints related to reproduction of the fish, including induction of vitellogenin in male fish, fewer broods per pair, and more eggs per brood. Parental exposure to as low as 0.0001 mg/L ibuprofen delayed hatching of eggs even when they were transferred to and cultured in clean water. Delayed hatching is environmentally relevant because this may increase the risk of being predated. For O. latipes, the acute-to-chronic ratio of ibuprofen was estimated to be greater than 1000. Overall, relatively high acute-to-chronic ratio and observation of reproduction damage in medaka fish at environmentally relevant ranges of ibuprofen warrant the need for further studies to elucidate potential ecological consequences of ibuprofen contamination in the aquatic environment.

Phototoxicity and oxidative stress responses in Daphnia magna under exposure to sulfathiazole and environmental level ultraviolet B irradiation

Sulfonamide antibiotics frequently occur in aquatic environments. In this study, phototoxicity of sulfathiazole (STZ) and its mechanism of action were investigated using Daphnia magna. We evaluated the changes of molecular level stress responses by assessing gene expression, enzyme induction and lipid peroxidation, and the related organism-level effects in D. magna. In the presence of ultraviolet B (UV-B) light (continuous irradiation with 13.8+/-1.0microWcm(-2)d(-1)), STZ (at the nominal concentration of 94.9mg/L) caused a significant increase in reactive oxygen species (ROS) generation and lipid peroxidation. Catalase (CAT) and glutathione S-transferase (GST) showed concentration-dependent increases caused by the exposure. Exposure to STZ and UV-B light caused apparent up-regulation of alpha-esterase, hemoglobin, and vitellogenin mRNA. The survival of daphnids was significantly affected by the co-exposure to STZ and UV-B. The biochemical and molecular level observations in combination with organism-level effects suggest that the phototoxicity of STZ was mediated in part by ROS generated by oxidative stress in D. magna.

Phototoxicity of CdSe/ZnSe quantum dots with surface coatings of 3-mercaptopropionic acid or tri-n-octylphosphine oxide/gum arabic in Daphnia magna under environmentally relevant UV-B light

The potential ecotoxicological consequences about semiconductor crystal nanoparticles (NPs) are a growing concern. However, our understanding of the mechanism of toxicity in NPs is very limited, especially under varying environmental conditions such as ultraviolet (UV) light. We performed an in vivo study employing Daphnia magna to evaluate the mechanism involved in toxicity of cadmium selenide/zinc selenide quantum dots (QDs) with two different organic coatings under an environmental level of UV-B light. We used QDs with mercaptopropionic acid (MPA) and tri-n-octylphosphine oxide/gum arabic (GA) and measured their toxicities under an environmental level of UV-B light. Whole-body reactive oxygen species (ROS) generation and mRNA expression level biomarkers, as well as acute toxicity, were measured in D. magna. With UV-B light, both cadmium (Cd) and GA-QD became more toxic in daphnids. The levels of small Cd molecules (<10kDa cutoff) increased for GA-QD under UV-B; however, the observed acute lethal toxicity could not be explained by the measured Cd level. Under UV-B light, both Cd and GA-QD generated more ROS. In addition, the expression pattern of mRNAs specific to Cd exposure was not observed from GA-QD with or without UV-B light. These observations suggest that the phototoxicity of QDs may be explained not only by Cd release from the QD core but also by stability of surface coating characteristics and other potential causes such as ROS generation.

Acute toxicity of two CdSe/ZnSe quantum dots with different surface coating in Daphnia magna under various light conditions.

With an increasing use of quantum dots (QDs) in many applications, their potential hazard is of growing concern. However, little is known about their ecotoxicity, especially in vivo. In the present study, we employed freshwater macroinvertebrate, Daphnia magna, to evaluate toxicity characteristics of cadmium selenide/zinc selenide (CdSe/ZnSe) in relation to surface coatings, e.g., mercaptopropionic acid QD (MPAQD), and gum arabic/tri‐n‐octylphosphine oxide QD (GA/TOPOQD), and light conditions, i.e., dark, fluorescent light, environmental level of ultraviolet (UV) light, and sunlight. The results of the present study showed that D. magna was more susceptible to GA/TOPOQD exposure compared to MPAQD. The surface coating of QD appeared to determine the stability of QDs and hence the toxicity, potentially by size change of or the release of toxic components from QDs. However, GA/TOPOQD was still less toxic than the equivalent level of CdCl2. The toxicity of all the tested compounds increased by changing the light condition from dark to white fluorescence to UV‐B light, and to natural sunlight. The effect of light condition on QDs toxicity could also be explained by photostability of the QDs, which would affect size of the particle, release of toxic component ions, and generation of reactive oxygen species. Considering increasing use of QDs in various applications, their environmental fates and corresponding toxic potentials deserve further investigation.

Perfluorooctane sulfonic acid exposure increases cadmium toxicity in early life stage of zebrafish, Danio rerio

Exposure to perfluorooctane sulfonic acid (PFOS) is known to induce thyroid-related adverse effects in aquatic organisms. Because an antioxidant defense mechanism is one of the key functions of the thyroid gland, we examined whether preexposure to PFOS could disrupt thyroid function and enhance cadmium (Cd)-induced oxidative stress in fish. Zebrafish embryos were exposed to control or 0.5 mg/L PFOS for 7 d after fertilization and subsequently exposed to 0.038 mg/L of Cd(2+) or a mixture of the PFOS and Cd for an additional 3 d until 10 d postfertilization (dpf). Survival rates, body length, messenger RNA (mRNA) expressions related to thyroid function and oxidative stress, the levels of thyroid hormones, and malondialdehyde and antioxidant enzyme activities were measured. Significant down-regulation of mRNAs related to thyroid function (thyroid hormone receptor-alpha [THRα], thyroid hormone receptor-beta [THRβ], hematopoietically expressed homeobox [hhex], and paired box gene 8 [pax8]) and decrease of throxine (T4) levels were observed in the PFOS preexposure group, suggesting that PFOS preexposure would influence the performance of thyroid gland in the later stages of life. Certain genes relative to oxidative stress, such as superoxide dismutase 1 (sod1) and heat shock protein 70 (hsp70), in the PFOS preexposure group were significantly up-regulated when the larvae were subsequently exposed to Cd or to the mixture of PFOS and Cd. Glutathione S-transferase activity and malondialdehyde levels of the PFOS-preexposed group were increased significantly by Cd exposure. Significant decrease of the survival rates and body length of fish were observed at 10 dpf among the larvae that were previously exposed to PFOS. These results suggest that preexposure to PFOS could affect antioxidant defense mechanisms and potentially increase the toxicity of Cd on mRNA expression and enzyme activity level responses, as well as on survival or growth of individuals.

Electron prebunching in microwave magnetron by electric priming using anode shape modification

Electric priming is proposed for electron prebunching in a microwave magnetron and is demonstrated using a particle-in-cell code. When the N∕2-fold perturbation of the radial electric field using an anode shape modification is imposed in the interaction space of the N-cavity magnetron along the azimuthal direction, the electrons initially develop into the desired π-mode resulting in rapid startup. The startup is hastened from 3.2 to 1.2 ns when the radial variation of the protrusion and recession is 6.5% of the anode radius with the angular width of 6°.

Stepwise Embryonic Toxicity of Silver Nanoparticles on Oryzias latipes

The developmental toxicity of silver nanoparticles (AgNPs) was investigated following exposure of Oryzias latipes (medaka) embryos to 0.1−1 mg/L of homogeneously dispersed AgNPs for 14 days. During this period, developmental endpoints, including lethality, heart rate, and hatching rate, were evaluated by microscopy for different stages of medaka embryonic development. To compare toxic sensitivity, acute adult toxicity was assessed. There was no difference in acute lethal toxicity between embryo and adult medaka. Interestingly, we found that the increase in stepwise toxicity was dependent on the developmental stage of the embryo. Lethal embryonic toxicity increased from exposure days 1 to 3 and exposure days 5 to 8, whereas there was no change from exposure days 3 to 5. In addition, 7 d exposure to 0.8 mg/L AgNPs resulted in significant heart beat retardation in medaka embryos. AgNPs also caused a dose-dependent decrease in the hatching rate and body length of larvae. These results indicate that AgNP exposure causes severe developmental toxicity to medaka embryos and that toxicity levels are enhanced at certain developmental stages, which should be taken into consideration in assessments of metallic NPs toxicity to embryos.

Non-monotonic concentration–response relationship of TiO2 nanoparticles in freshwater cladocerans under environmentally relevant UV-A light

The effects of UV-A on the toxicity of TiO2 nano-particles (NPs) were evaluated using Moina macrocopa and Daphnia magna under environmentally relevant level of UV-A. The waterfleas were exposed to TiO2 NPs with different sizes of ~298nm, ~132nm, or ~72nm for up to 48h, with or without UV-A light. Whole body reactive oxygen species and transcription of antioxidant enzyme genes were measured, as well as the survival of the waterflea. In the presence of UV-A, the survival rates of M. macrocopa significantly decreased in concentration dependent way until ~1mg/L TiO2 NPs, but the survivals were reversed at greater concentrations. This peculiar non-monotonic trend of concentration-response relationship might be explained by changes of particle size under different light conditions. TiO2 NPs within a certain size range could be trapped in the filter apparatus and exert toxicity, and the NPs of greater size were subject to either precipitation or ingestion leading to no or little toxicity. Observed TiO2 toxicity was associated with oxidative stress in the filter apparatus. The results of this study showed that the size change due to UV-A irradiation should be considered in evaluation of ecological risks of TiO2 NP.

Reduction of noise in strapped magnetron by electric priming using anode shape modification

Noise reduction in a 2.45GHz strapped magnetron oscillator is experimentally demonstrated by electric priming using anode shape modification. The sideband noise is reduced by approximately 15dB at the nominal operating current and by 28dB at the start-oscillation current; this is due to electron prebunching into the π mode, resulting from the modulation of the drift velocity of the electrons by an azimuthally periodic electric field. In this experiment, a 4.3kV–330mA half-wave rectified input power is employed.

Soluble c‐Met protein as a susceptible biomarker for gastric cancer risk: A nested case‐control study within the Korean Multicenter Cancer Cohort

This study was conducted to evaluate the relevance of the soluble form of c‐Met protein, a truncated form of the c‐Met membrane receptor involved in the CagA pathway, as a potential biomarker for gastric cancer. Among 290 gastric cancer case‐control sets selected from the Korean Multicenter Cancer Cohort, the plasma concentrations of soluble c‐Met protein were measured with enzyme‐linked immunosorbent assays. Using analysis of variance and covariance models with age, sex, smoking, Helicobacter pylori infection, and CagA seropositivity, the mean concentrations of soluble c‐Met protein between cases and controls were compared. To evaluate the association between gastric cancer and a c‐Met protein level, odds ratios and 95% confidence intervals were estimated using conditional logistic regression models. Interactions between CagA‐related genes and the soluble c‐Met protein concentration were also investigated. The overall median plasma concentration of soluble c‐Met among cases was significantly lower than those of controls (1.390 vs. 1.610 ng/mL, p < 0.0001). Closer to the onset of gastric cancer, the soluble c‐Met protein level decreased linearly in a time‐dependent manner (p for trend = 0.0002). The combined effects between the CagA‐related genes and the soluble c‐Met protein concentration significantly intensified risks for gastric cancer. Restricted analyses including cases that had been diagnosed within 1 year after entering the cohort had a fair degree of ability (area under the receiver operating characteristic curve of 0.73–0.77) to discriminate gastric cancer cases from normal controls. Our findings demonstrate the potential of the soluble form of c‐Met protein as a novel biomarker for gastric cancer. The beneficial effects of a high soluble c‐Met concentration in human plasma are strongly supported.