• Environmental Analysis Health and Toxicology
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• v.22 no.4
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• pp.305-312
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• 2007

환경오염을 신속하게 모니터링하기 위한 생물지표의 개발은 증가하고 있는 오염의 심각성에 비추어 매우 중요한 과제로 여겨지고 있다. 본 연구에서는 독성물질처리에 의하여 선택적으로 발현이 조절되는 단백질의 동정을 통하여 독성물질에 대한 단백질 생물지표를 발굴하고자 시도하였다. 즉, 송사리(Oryzias latipes)를 유기인계 살충제인 다이아지논(diazinon)에 0, 0.1, 1, 5 mg/L 농도로 24시간 노출시킨 후, 머리와 몸통부분으로 나누어 단백질 발현패턴을 분석하였다. 본 시스템에서 다이아지논 처리에 의하여 유의적으로 발현이 증가된 단백질로서 alpha-tubulin, ribonuclease pancreatic precursor, protein hfq 등을 동정하였으며, 이 가운데 alpha-tubulin과 $hsp90{\beta}$의 발현이 다이아지논 농도에 의존적으로 증가하는 것을 semi-quantitative RT-PCR방법으로 확인하였다. 이와 같이 다이아지논 처리에 특이적으로 발현이 증가된 송사리 단백질들은 노출평가를 위한 생물지표로서 개발에 응용될 수 있을 것으로 평가된다.

• The Korean Journal of Ecology
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• v.21 no.3
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• pp.225-231
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• 1998

The studies on the potentiality of biomonitoring heavy metal pollution in coastal region of industrial complex were performed to investigate the heavy metal accumulation and induction of metal-binding protein (MBP) as detoxification process using Rumex maritimus. Bioconcentration in organs and MBP in root of R. maritimus was investigated for the research of the tolerance of heavy metals. The bioconcentration of cadmium and zinc in organs showed 3.6-8.0 times in root higher than in shoot, so it was found that heavy metal accumulated selectively in root. MBP increased absorbance in 254 nm and decreased in 280 nm, because it was composed of high cystein content and low aromatic acids, so absorbance had large difference between 254 nm and 280 nm. The existence of MBP in the 10-20 fraction was ascertained with anion exchange chromatography and it was identified that concentration of heavy metal increased according as an exposure concentration of medium increased in QAE Sephadex A-25 elution profile. These results suggested that MBP could play a role in biomarker determining the bioconcentration of plant. This study demonstrated a possibility that removal ability of heavy metal of R. maritimus resulted from detoxification process and MBP could be utilized as a biomarker of heavy metal pollution.

• Molecular & Cellular Toxicology
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• v.1 no.2
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• pp.106-110
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• 2005

N-ethyl-N-nitrosourea (ENU), which is a toxin and a carcinogen, as well as a mutagen, has a variety of effects on mice. ENU induces point mutation in male germ cell. Number of mutant animals are developed with ENU treatment. However, potentiality ot ENU as a carcinogen is not fully understood, even though, mutagenicity of ENU is broadly studied, In the present study, the gene expression profiling and histopathological investigation of ENU treated mouse's liver and brain were investigated. Also, the expression patterns of cancer related genes in ENU-treated mouse were analyzed.

• Toxicological Research
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• v.13 no.3
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• pp.257-263
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• 1997

Pentachlorophenol(PCP) which ks widely used in wood preservation, pulp and paper mills, has led to a substantial envirortmental contamination. To get the reliable data for the effective health risk assessment with PCP, covalent binding potential of PCP to cellular macromolecules and glutathione(GSH) was investigated after intraperitoneal administration of $^{14}C-PCP$ to rats. PCP metabolites were able to bind covalently to serum albumin and hepatic protein in a dose- and time-dependent manner. Hepatic protein adducts of PCP metabolites were increased as a function of cytochrome P-450 activities, whereas, albumin adducts significantly decreased. Covalent binding of PCP metabolites with DNA or hemoglobin was not observed. GSH levels in liver tissue decreased over 12hrs, however, the level was recovered after 48hrs. Tetrachloro-1,4-benzoquinone (1,4-TCBQ), one of the most reactive PCP metabolites, conjugated with GSH very rapidly. Base on our results, we could conclude that PCP metabolized to reactive electrophilic metabolites by cytochrome P-450 isoenzymes and conjugated rapidly with neighboring protein or nonprotein sulfhydryl before reacting with DNA or hemoglobin. We propose that albumin adducts and mercapturic acids of PCP metabolites can be used good biomarker of recent PCP exposure.

• Fisheries and Aquatic Sciences
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• v.6 no.2
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• pp.74-80
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• 2003

Two cellular biomarker parameters of the farmed Pacific oyster Crassostrea gigas were studied in vivo and in vitro after exposure to concentrations of polychlorinated biphenyls in terms of neural red uptake (NRU) and lysozyme activity. The oysters exposed in vivo to the xenobiotic concentrations, 0, 30, 90, and 180 ng/g for 14 days, enhanced hemocyte NRU with occasional significant differences (P<0.05), depending on the chemical concentration and duration. An adverse tendency was manifest in the lysozyme activities both in the hemocyte and serum of the oyster treated with the chemical in a same manner, rendering these two cellular parameters as biomarker candidates against the chemical. The oysters exposed in vitro to the chemical concentrations, 0, 1, 5, 10, 100, 1,000, and 10,000 ng/g for 24 hrs at $10^{\circ}C$ showed a similar tendancy as those exposed in vivo to the chemical. Unlike in vivo response, however, the in vitro NRU was first influenced by very low concentration of the chemical. In in vitro results, marked but not significant increase of hemocyte NRU was noticed at the chemical concentration of 5 ng/g, where the value was almost as high as those exposed to higher chemical concentrations, up to 10,000 ng/g. An unusual result was observed in the in vitro lysozyme activity of hemocyte in which significant decrease was first noticed at the chemical concentration of 100 ng/g.

• Toxicological Research
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• v.26 no.1
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• pp.21-28
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• 2010

As the frequency and the intensity of so called Asian dust (AD) events have increased, public concerns about the adverse health effects has spiked sharply over the last two decades. Despite the recent reports on the correlation between AD events and the risk for cardiovascular and respiratory disease, the nature of the toxicity and the degree of the risk are yet largely unknown. In the present study, we investigated the effects of the dichloromethane extract of AD (AD-X) and that of urban dust (NAD-X) collected during a non-AD period on gene expression in HL-60 cells using Illumina Sentrix HumanRef-8 Expression BeadChips. Global changes in gene expression were analyzed after 24 h of incubation with 50 or 100 ${\mu}g$/ml AD-X and NAD-X. By one-way analysis of variance (p < 0.05) and Benjamini-Hochberg multiple testing correction for false discovery rate of the results, 573 and 297 genes were identified as AD-X- and NAD-X-responsive, respectively. The genes were classified into three groups by Venn diagram analysis of their expression profile, i.e., 290 AD-X-specific, 14 NAD-X-specific, and 283 overlapping genes. Quantitative realtime PCR confirmed the changes in the expression levels of the selected genes. The expression patterns of five genes, namely SORL1, RABEPK, DDIT4, AZU1, and NUDT1 differed significantly between the two groups. Following rigorous validation process, these genes may provide information in developing biomarker for AD exposure.

• Genomics & Informatics
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• v.2 no.2
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• pp.75-80
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• 2004

In a variety of animal species, the perinatal exposure of experimental animals to the 2,3,7,8-tetrachlorodibenzo­p-dioxin (TCDD) leads to the immune dysfunction, which is more severe and persistent than that caused by adult exposure. We report here the changes of gene expression and the identification of the marker-genes representing the dioxin exposure. The expressions of the transcripts were analyzed using the 11 K oligonucleotide­microarray from the bone marrow cells of male C57BL/6J mice after an intraperitoneal injection of $1{\mu}g$ TCDD/kg body weight at various time intervals: gestational 6.5 day(G6.5), 13.5 day(G13.5), 18.5 day(G18.5), and postnatal 3 (P3W)and 6 week (P6W). The type of self-organizing maps(SOM) representing the specific exposure dioxin could be identified as follows; G6.5D(C14), G13.5D(C0, C5, C10, C18), G18.5D(7): P3W(C2, C21), and P6W(C4, C15, C20). The candidate marker-genes were restricted to the transcripts, which could be consistently expressed greater than $\pm$2-fold in three experiments. The resulting candidates were 85 genes, the characteristics of that were involved in cell physiology and cell functions such as cell proliferation and immune function. We identified the biomarker-genes for dioxin exposure: smc -like 2 from SOM C14 for the dioxin exposure at G6.5D, focal adhesion kinase and 6 other genes from C0, and protein tyrosine phosphatase 4a2 and 3 other genes from C5 for G13.5D, platelet factor 4 from C7 for G18.5D, fos from C2 for P3W.

• Biomedical Science Letters
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• v.11 no.4
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• pp.509-515
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• 2005

This study was conducted to determine the kinetics of cyclohexane metabolites (the biomarker on cyclohexane exposure), the changes of hepatic cyclohexane metabolizing enzyme activities and the metabolites of cyclohexane in urine or serum. The rats were sacrificed at 2, 4, 8, 12 and 24 hr after administration of one dose of cyclohexane (1.56 g/kg body weight, i.p.). The metabolites of cyclohexane in urine were identified as cyclohexanol, cyclohexanone, trans-l,2-cyclohexanediol and 1,4-cyclohexanediol with cyclohexane metabolite being 124.00, 0.78, 23.28 and 2.75 (g/g of creatinine, $1\times10^{-3}$). Most of the cyclohexanol and trans-l,2-cyclohexanediol were determined to be in the form of $\beta-glucuronide$ conjugates, whereas cyclohexanone and 1 ,4-cyclohexanediol were found as free forms. In toxicokinetics of serum cyclohexane metabolites, cyclohexanol showed a rapid increase, reaching the plateau at 4 hr, after this time rapidly decreased throughout 24 hr. Changes of cyclohexanone also showed the similar pattern with cyclohexanol except somewhat lower concentration. Trans-l,2-cyclohexanediol, however, showed a gradual increase until 12 hr with the continued same levels throughout 24 hr. On the other hand, 1,4-cyclohexanediol was detected as trace levels at 4 and 12 hr, respectively. The administration of cyclohexane led to a significant increase of hepatic aniline hydroxylase activity from 2 to 8 hr. The activity of hepatic alcohol dehydrogenase showed a significant increase at 4 hr and then were recovered to the level of the control at 24 hr. On the other hand, there were no differences in liver weightlbody weight between the control and cyclohexane-treated animals. However, there were the changes of aniline hydroxylase and alcohol dehydrogenase activities on time-dependent pattern after cyclohexane treatment, which influence on the degree of cyclohexane metabolites both in blood and urine. These results suggest that differential determination of cyclohexane metabolites in urine and serum may be able to be as a biomarker of cyclohexane-exposure in the body. But in this fields further study is needed.

• Journal of Preventive Medicine and Public Health
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• v.28 no.2 s.50
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• pp.406-420
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• 1995

To study the health hazards and exposure status of manganese among female manganese workers, authors conducted airborne, blood and urine manganese concentration measurements, questionnaire and neurological examinations on 80 manganese-handling productive female workers(exposed group) in a manganese manufacturing facto in Pohang city and 127 productive female workers not handling manganese(control group) in other factories in the Pohang city. The results are; 1. Geometric mean concentrations of manganese in air and urine were $0.98mg/m^3\;and\;4.12{\mu}g/l$ and arithmetic mean concentration of manganese in blood was $6.94{\mu}g/dl$ in exposed group, significantly higher than those of control group(p<0.05). However, clinical and laboratory findings in exposed group were not statistically different from those of control group. 2. As age increase, positive rates of clinical symptoms also increased in the exposed group. However, in older aged group, the positive rates of symptoms and signs were statistically different from those of control group. We observed the same tendency in the positive rates of the neurological examinations. 3. There was statistically significant correlation between airborne and urine manganese concentrations(r=0.61, p<0.01) while there was no statistically significant correlation between airborne and blood manganese concentrations(r=0.29, p>0.05). The results suggest that urine manganese concentration was the best appropriate biomarker to estimate the exposure to manganese in respect to clinical symptoms and signs. In the analysis of correlation between urine and airborne manganese concentrations, it is required to adjust the present permissible exposure level(PEL) of airborne manganese.

• Journal of Aquaculture
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• v.18 no.3
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• pp.173-179
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• 2005

Superoxide dismutase (SOD), an antioxidant enzyme catalyzing the first step for scavenging the reactive oxygen species is important as an early warning indicator to address various biological stresses. For this reason, the monitoring the expressed pattern of SOD gene in fish organs is one of important biomarkers to assess the aquatic pollution caused by many toxic chemicals. Based on the Northern blot hybridization, semi-quantitative and/or realtime RT-PCRs, the alteration of SOD gene transcripts in shark liver was examined during the experimental acute exposures to cadmium. The expression of SOD at mRNA level was up-regulated both by injection (0, 0.5, 1 or 2 mg $CdCl_2/kg$ body weight for 48 hours) and by immersion (0 or $5{\mu}M$ Cd for 0, 1, 4 and 7 days) treatments of cadmium. The transcriptional stimulation of shark SOD gene by cadmium exposure was dependent upon doses and durations: there was a trend toward more increase in higher dose and longer durations of exposure. The hepatic SOD mRNA levels showed also a general agreement with the tissue cadmium concentrations accumulated in immersion exposure. This result may provide useful strategy to develop a fine molecular biomarker at mRNA level for detecting aquatic pollution caused by toxic metals.