A comprehensive model of electrical noise in AlGaAs/GaAs long-wavelength quantum well infrared photodetectors.

We present the results of a comprehensive model for the electric noise simulation of a kind of nano-optoelectronics device: AIGaAs/GaAs long-wavelength quantum well infrared photodetectors (LW-QWIPs) in dark conditions by assuming a three-dimensional carrier transport in the barriers where the electrical field are obtained in a self-consistent way. This model takes into account all the fundamental mechanisms involved in the device detection process. The electrical field distribution, dark currents, electrical noise are carefully calculated and analyzed. The numerical results also explain well our experimental observations.

Comparative chronic liver toxicity of benzo[a]pyrene in two populations of the atlantic killifish (Fundulus heteroclitus) with different exposure histories.

BACKGROUND: The Atlantic Wood Industries Superfund site on the Elizabeth River (ER) in Portsmouth, Virginia, is contaminated with polycyclic aromatic hydrocarbons (PAHs) derived from creosote. Embryos and larvae of ER killifish (Fundulus heteroclitus) are refractory to the induction of enzymes regulated by the aryl hydrocarbon receptor including cytochrome P4501A (CYP1A) and are resistant to PAH-induced lethality and teratogenicity. However, adult ER killifish show a greater prevalence of hepatic and pancreatic tumors compared with those from reference sites. OBJECTIVES: We used controlled laboratory studies to determine if ER killifish are more or less sensitive to PAH-induced chronic hepatic toxicity than killifish from an uncontaminated site. METHODS: Larvae from the ER and a reference site on King's Creek (KC) were subjected to two 24-hr aqueous exposures of benzo[a]pyrene (BaP; 0-400 µg/L). At various time points, larvae were analyzed for CYP1A activity, BaP concentrations, nuclear and mitochondrial DNA damage, and liver pathology. RESULTS: CYP1A activity was induced by BaP in KC but not ER larvae, and KC larvae demonstrated a greater reduction in whole-body concentrations of BaP over time. Mitochondrial and nuclear DNA lesion frequency increased significantly in BaP-exposed KC larvae, but not in ER larvae. Nine months postexposure, KC juveniles exhibited significantly more hepatic foci of cellular alteration and only KC juveniles developed hepatocellular carcinomas. CONCLUSIONS: In addition to acquiring the heritable resistance to the acute teratogenic effects of PAHs, ER fish appear to have concomitantly developed resistance to chronic effects, including cancer.

Effect of CYP1A inhibition on the biotransformation of benzo[a]pyrene in two populations of Fundulus heteroclitus with different exposure histories.

Sediment contaminated with polycyclic aromatic hydrocarbons (PAHs) from a Superfund site on the Elizabeth River (ER) in Portsmouth, VA, is teratogenic to embryonic killifish (Fundulus heteroclitus) from reference sites. However, embryos born to a population of ER killifish are resistant to PAH-induced teratogenicity. Mechanisms underlying the resistance are unclear; however, ER killifish are refractory to induction of metabolic enzyme cytochrome P4501A (CYP1A), at the level of mRNA, protein and activity. The contaminated ER sediment comprises a complex mixture of PAHs with different mechanisms of toxicity. While many are inducers of metabolic enzymes involved in both phase I and phase II of biotransformation, some PAHs can also inhibit phase I enzymatic activity. Previous research has shown that co-exposure to PAHs with different modes of action can result in synergistic embryotoxicity (Billiard, S.M., Meyer, J.N.D., Wassenberg, M., Hodson, P.V., Di Giulio, R.T., 2008. Nonadditive effects of PAHs on early vertebrate development: mechanisms and implications for risk assessment. Toxicological Sciences 105, 5-23). Two of the abundant PAHs at the ER are fluoranthene (FL), a CYP1A inhibitor, and benzo[a]pyrene (BaP), a CYP1A inducer. Based on the ER resistant phenotype and the PAH mixture in the ER sediment, we hypothesized that the inhibition of CYP1A activity affects the teratogenicity of PAHs through a biotransformation-mediated mechanism. To examine this hypothesis, we compared the responses of killifish embryos born to parents from the ER and from a reference site (King's Creek (KC), VA) after a water-borne exposure to BaP (0-400 microg/L) in the presence or absence of FL (0-500 microg/L). Embryos were dosed from 24 to 120 h post-fertilization (hpf) and were analyzed for induction of CYP1 enzymatic activity as measured by the ethoxyresorufin-O-deethylase (EROD) assay, cardiac deformities, and BaP metabolic profile. KC embryos showed significant induction of CYP1 protein activity at all BaP concentrations examined. Co-exposure to 500 microg/L of FL significantly decreased CYP1 activity and increased cardiac deformities. ER embryos showed no change in CYP1 activity or cardiac deformities for any treatment. Significantly greater concentrations of BaP and BaP 9,10-dihydrodiol were recovered from ER embryos compared to those from KC. Co-exposure with FL did not significantly alter the amount of BaP or the metabolites recovered in either population. These findings suggest that the teratogenicity observed by co-exposure to BaP and FL cannot fully be explained by alteration in BaP metabolism. This study also indicates that the metabolic adaptation observed in the ER killifish cannot be explained simply by the refractory CYP1 phenotype.

Urinary excretion study of coenzyme Q10 in rats by ultra-performance liquid chromatography-mass spectrometry.

A method based on ultra-performance liquid chromatography mass spectrometry (UPLC-MS) applying atmospheric pressure chemical ionization in the positive ion mode is developed for the determination of coenzyme Q10 (CoQ10) in rat urine. The assay involves the extraction of crude urine, fast liquid chromatography on a Waters Acquity UPLC BEH C18 column (1.7 microm, 1.0 x 50 mm), and selected ion monitoring detection using mass transition. The calibration range is found to be 0.05-25 microg/mL, with the lower limit of quantitation of 0.05 microg/mL. Intra- and inter-day precision (relative standard deviation) for CoQ10 in rat urine range from 0.7% to 15%, and accuracy expressed in recovery rates in urine is between 83% and 118%. The recovery of this method is found to be between 80% and 95% at three concentrations. The total cumulative recovery of CoQ10 is 1.16 +/- 1.05% (percentage of dose intake, n = 4) from rat urine collected over 30 h after oral administration of the drug. The UPLC-MS method described allows the quick determination of CoQ10 in rat urine with good precision and accuracy. It is suitable for further excretion studies of CoQ10 in animals.

Simultaneous determination of benzo[a]pyrene and eight of its metabolites in Fundulus heteroclitus bile using ultra-performance liquid chromatography with mass spectrometry.

A sensitive and fast method was developed to quantitate the carcinogenic polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP) and eight of its oxidized metabolites by ultra-performance liquid chromatography (UPLC) coupling with mass spectrometry (MS). The UPLC method, using an acetonitrile:water gradient as a mobile phase, provided baseline separation of the BaP metabolites including three BaP diones. Linearity of detection was in the range of 0.2-5.0ng/microL, and limits of detection (LOD) were lower than 0.01ng/microL for BaP and all of the metabolites except BaP tetrol. In order to test this method in environmentally relevant samples, we exposed the small fish Fundulus heteroclitus to BaP and quantitated biliary BaP metabolites. Extraction recovery of all compounds varied from 65.4+/-21.3% to 92.4+/-3.0%. In exposed fish bile, the BaP diones, BaP-7,8-dihydrodiol, and 3-hydroxy BaP metabolites predominated, existing mainly as glucuronic acid conjugates. This UPLC-MS method will be useful for further defining the roles of cytochrome P450s with both in vivo and in vitro models in the understanding of the mechanisms of metabolic activation and detoxification of BaP.

Biomarker induction in tropical fish species on the Northwest Shelf of Australia by produced formation water.

Normal operation of oil well platforms results in the discharge of produced formation water (PFW). The expression of CYP1A, CYP2M1- and 2K1-like proteins was examined for use as possible biomarkers of PFW exposure. A pilot study on the Northwest Shelf of Australia had indicated that PFW contamination possibly contributes to induction of CYP1A-like proteins in Gold-Spotted Trevally (Carangoides fulvoguttatus). The pilot study samples were re-examined for CYP1A, and, in addition, CYP2K1/2M1-like proteins. In a subsequent caged fish study in the same location a second species, Stripey seaperch (Lutjanus carponotatus), caught at a clean site, were distributed to three caging sites in a PFW gradient from the Harriet A production platform: A (near-field), B (far-field) and C (a non-impacted reference site). Fish were sampled at time (T) T = 0, T = 3 and T = 10 days. Significant increases of CYP1A, one CYP2K1- and two CYP2M1-like proteins were noted at Site A at T = 10d. For another CYP2K1-like protein, a significant increase was observed at Site A only at T = 3d. These results support a previous study indicating that CYP1A protein is sensitive to PFW exposure. Importantly, statistically significant environmental induction of both CYP2M1- and CYP2K1-like proteins in tropical fish due to PFW exposure had not previously been described and induction of enzymes in the CYP2 family suggest new biomarkers for PFW. In addition, the novel response of one CYP2K-like protein requires further verification, but offers promise for improved monitoring of sub-lethal responses in marine organisms.

Ethanol attenuates Aldh9 mRNA expression in Japanese medaka (Oryzias latipes) embryogenesis.

The mechanisms of teratogenic effects of ethanol in Japanese medaka embryogenesis were investigated by testing the hypothesis that ethanol or its metabolite ameliorates the expression of ethanol metabolizing enzymes. We have previously demonstrated that ethanol is unable to alter the expression pattern of alcohol dehydrogenase (ADH) mRNA, the first enzyme of ethanol metabolism, in medaka embryos during development. We, therefore, extended our investigation to aldehyde dehydrogenase (ALDH) system, the next enzyme of alcohol metabolic pathway. As the first step towards studying the regulation of Aldh mRNA expression by ethanol, we have cloned a cDNA by reverse transcriptase polymerase chain reaction (RT-PCR) from adult Japanese medaka (Oryzias latipes) liver representing the medaka ALDH9 gene product, with a coding region of 1515 nucleotides. The deduced amino acid sequences share 81.2% identity with cod liver betaine aldehyde dehydrogenase (BADH, EC 1.2.1.8), and 71.1% identity with human ALDH9A1 sequences. RT-PCR analysis further showed that in adults Aldh9 mRNA is constitutively expressed in all organs tested (brain, eye, gill, GI, heart, liver, kidney, muscle, skin, testis and ovary). Using semi-quantitative (rRT-PCR) and quantitative real time RT-PCR (qRT-PCR), we detected Aldh9 mRNA at all time points of development and the expression was lowest between approximately 1 and 8 h post-fertilization (hpf). Treatment of the embryos with ethanol for 48 h post-fertilization (hpf) attenuates (delayed) the expression of Aldh9 mRNA. This delayed expression of Aldh9 mRNA by ethanol may enhance acetaldehyde concentration in the embryo and induce teratogenesis during development.

Toxicity of an engineered nanoparticle (fullerene, C60) in two aquatic species, Daphnia and fathead minnow.

Water-soluble fullerene (nC60) has been shown to induce lipid peroxidation (LPO) in brain of juvenile largemouth bass (LMB, Micropterus salmoides) [Oberdörster, E., 2004. Manufactured nanomaterials (fullerenes, c60) induce oxidative stress in brain of juvenile largemouth bass. Environ. Health Persp. 112, 1058-1062]; and upregulate genes related to the inflammatory response and metabolism, most notably CYP2K4 [. Nanotoxicology: an emerging discipline evolving from 116 studies of ultrafine particles. Environ. Health Persp. 113, 823-839]. The initial study in LMB was performed using tetrahydrofuran (THF)-solubilized nC60, although C60 can also be solubilized by stirring in water. The current study investigates differences in acute toxicity to Daphnia magna between THF-solubilized and water-stirred-nC60 as a range-find for further assays in adult male fathead minnow (FHM, Pimephales promelas). The daphnia 48-h LC50 for THF-nC60 was at least one order of magnitude less (0.8 ppm) than that for water-stirred-nC60 (> 35 ppm). FHM were dosed with either 0.5 ppm of THF- or water-stirred-nC60 for 48 h. There was 100% mortality in the THF-nC60-exposed fish between 6 and 18 h, while the water-stirred-nC60-exposed fish showed no obvious physical effects after 48 h. Water-stirred-nC60 elevated LPO in brain, significantly increased LPO in gill, and significantly increased expression of CYP2 family isozymes in liver as compared to control fish.

Environmental induction of CYP1A-, CYP2M1- and CYP2K1-like proteins in tropical fish species by produced formation water on the northwest shelf of Australia.

Normal operation of oil well platforms results in the discharge of "produced formation water" (PFW). The expression of CYP1A, CYP2M1- and 2K1-like proteins was examined for use as possible biomarkers of PFW exposure. A pilot study at the Harriet A production platform, on the Northwest Shelf of Australia, had indicated that PFW contamination possibly contributes to induction of CYP1A- and 2K1/2M1-like proteins in Gold-Spotted Trevally (Carangoides fulvoguttatus). In a subsequent caged fish study in the same location, Stripey seaperch (Lutjanus carponotatus) were caught at a clean site, then distributed to three caging sites: A (near-field), B (far-field) and C (a non-impacted reference site). Fish were sampled at time T = 0, 3 and 10 days. Significant increases of CYP1A, one CYP2K1- and two CYP2M1-like proteins were noted at Site A at T = 10. For another CYP2K1-like protein, a significant increase was observed at Site A only at T = 3. Prevailing winds changed between days 6 and 8 of sampling, moving the surface water plume directly west, possibly impacting in situ PFW exposure. The results indicate that tropical fish CYP1A protein is sensitive to PFW exposure. Importantly, statistically significant environmental induction of both CYP2M1- and CYP2K1-like proteins in tropical fish due to PFW exposure had not previously been described and CYP2 family induction may represent possible new biomarkers (other than CYP1A) of PFW exposure. In addition, the novel fraction-specific response of CYP2K-like proteins requires further verification but offers promise for improved monitoring of sub-lethal responses in marine organisms. (Supported by Australian Institute of Marine Science, Apache Energy Ltd. and the Environmental Toxicology Research Program at The University of Mississippi).