• Toxicological Research
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• 제17권
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• pp.323-327
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• 2001

March 19, 1999, the renovation qf the runway of the Bo-Fai ai1field in Hua Hin, Prachubk-erikhan, Thailand, unearthed chemicals which were left over from the project "anch Hand Operation" held during the Vietnam war era. The chemical mixtures were analyzed by the US EPA, the Department oj Medical Sciences (DMSc), Ministry oj Public Health (MoPH) and the Pollution Control Department (PCD), the Ministry oj Science Technology and Environment (MOSTE) of Thailand, The samples were found to contain several defoliants used in the operation. They were 2,4-D, 2,4,5-T, Dicamba, Cocydelic acid, and Dioxins. Due to the complexity of the issue, the multiplicity of possible health effects, and the socio-economic implications for imports and exports, the Thai Society of Toxicology submitted a proposal to request World Health Organization (WHO), Geneva. The assistance is for the area of chemical safety and called for immediate action to explore the magnitude qf risk involved with Dioxins. In this paper we present our approach to health risk assessment which takes into an account the epidemiological studies of high-risk group exposed to the Ranch Hand operation. Dioxins are endocrine disruption chemicals which public concerns are developed due to presumption that a hazard exists (www.eva.gov/dioxins/html) for which current methodologies are deemed insufficient. The recent concepts of how oxidative stress toxicants may affect health end points and biomarkers of exposure of exposed individuals are discussed. While research activities are undergoing, The Thai Society of Toxicology do not anticipate significant risk to local residents and the environment due to our concurrence with opinion from the international experts invited by the World Health Organization proposed to the local experts at a workshop in Bangkok.n Bangkok.

• Toxicological Research
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• 제26권3호
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• pp.203-208
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• 2010

Bronchoalveolar lavage (BAL) is a useful tool in researches and in clinical medicine of lung diseases because the BAL fluid contains biochemical and cytological indicators of the cellular response to infection, drugs, or toxicants. However, the variability among laboratories regarding the technique and the processing of the BAL material limits clinical research. The aim of this study was to determine the suction frequency and lavage fraction number necessary to reduce the variability in lavage using male Sprague-Dawley rats. We compared the total cell number and protein level of each lavage fraction and concluded that more cells and protein can be obtained by repetitive lavage with a suction frequency of 2 or 3 than by lavage with a single suction. On the basis of total cell recovery, approximately 70% of cells were obtained from fractions 1~3. The first lavage fraction should be used for evaluation of protein concentration because fractions 2~5 of lavage fluid were diluted in manifolds. These observations were confirmed in bleomycin-induced inflamed lungs of rats. We further compared the BAL data from the whole lobes with data from the right lobes and concluded that BAL data of the right lobes represented data of the whole lobes. However, this conclusion can only be applied to general lung diseases. At the end, this study provides an insight into the technical or analytical problems of lavage study in vivo.

• Ocean and Polar Research
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• 제28권1호
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• pp.45-56
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• 2006

This study investigated primarily the toxic effects of bis(tributyltin)oxide (TBT) and DDT (Dichlorodiphenyltrichloroethane) on the mortality of adult Acartia omorii and barnacle nauplii as well as the hatching rate of A. omorii. Subsequently, compound effects of TBT and DDT on the mortality of immature copepods were tested in order to assess whether or not synergistic influence existed in the mixture of sublethal concentration of two pollutants. Mortality of adult A. omorii increased as exposure concentration of DDT increased in the range of from 0.0001 to 1ppm. Egg hatching rate of the copepod showed no distinctive difference in the range between 0.1 and 10ppm, while barnacle nauplii showed abnormal motility of their appendages in the range of 0.0001 to 1 ppm. Mortality of adult A. omorii increased as TBT concentration increased within the range of 1 and 10 ppb, whereas egg hatching rate of the copepod showed no linear response to the same exposure range. Moreover, copepod nauplii were almost motionless even though copepod eggs hatched under the exposure condition of TBT $(0{\sim}10 ppb)$ and DDT $(0{\sim}10 ppm)$, respectively, suggesting that the nauplii are hard to develop into adult stage. On the basis of the sublethal concentration less than the 24-h $LC_{50}$, 0.001 ppm (DDT) and 2 ppb (TBT) were selected to confirm the compound effects of two pollutants on the mortality of immature copepods. Mortality of immature copepods under the condition of mixture of the two pollutants was higher than that in the single exposure condition. This result seems to indicate that synergistic effects of sublethal toxicants can make a more hazardous effect on the survival of immature copepods even though the concentration of single toxicant is not lethal to copepods in the marine environment.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7555-7560
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• 2013

Background: Beedi rollers are exposed to unburnt tobacco dust through cutaneous and pharyngeal route and it is extremely harmful to the body since it is carcinogenic in nature and can cause cancer during long exposure. This indicates that occupational exposure to tobacco imposes considerable genotoxicity among beedi workers. Materials and Methods: In the present study, 27 beedi workers and age and sex matched controls were enrolled for clinical, cytogenetics and molecular analysis. Clinical features were recorded. The workers were in the age group of 28-67 years and were workers exposure from 8-60 years. Blood samples were collected from workers and control subjects and lymphocyte cultures were carried out by using standard technique, slides were prepared and 50 metaphases were scored for each sample to find the chromosomal abnormalities. For molecular analysis the genomic DNA was extracted from peripheral blood, to screen the variations in gene, the exon 1 of CYP1A1 gene was amplified by polymerase chain reaction (PCR) and then screened with Single Strand Conformation Polymorphism (SSCP) analysis. Results: A statistically significant increase was observed in the frequencies of chromosomal aberrations in exposed groups when compared to the respective controls and variations observed in Exon 1 of CYP1A1(Cytochrome P450, family 1, subfamily A, polypeptide 1) gene. Conclusions: This study shows that, the toxicants present in the beedi that enter into human body causes disturbance to normal state and behavior of the chromosomes which results in reshuffling of hereditary material causing chromosomal aberrations and genomic variations.

• 한국물환경학회지
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• 제20권1호
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• pp.48-54
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• 2004

Two methods, a Ceriodaphnia algal uptake suppression test (CAUST) and a new toxicity test based on temperature control (TTBTC) which are based on feeding behaviour and temperature control, respectively, were developed and compared for the adoption as the better methodology for short-term toxicity screening. As previously published by Lee et aI., (1997), the CAUST method is based on the feeding behaviour of C. dubia and requires as little as 1 hour of contact time between C. dubia neonates and toxicant. However, even though CAUST requires only 1 hour of contact time, this method still take many hours for the preparation and measurement. Before the test starts, neonate digestive tracts were cleared by feeding yeast to the daphnids, Neonates were then exposed to toxicant, followed by addition of Scenedesmus subspiatus into the bioassay vessels. Daphnids were examined under the bright-field microscope with the presence of algae (indicated by a green colored digestive tract) or the absence of algae. Uptake indicated no toxic effect, whereas, absence of uptake indicated toxic inhibition. Unlike CAUST, the newly developed method (TTBTC) is based on just temperature control for the toxicity test of C. dubia. Initially, neonates are exposed to toxicants while the temperature of water bath containing media increased to $35.5^{\circ}C$. After 1.25 hour of contact time, the number of the daphnids, either live (no toxic effect) or dead (toxic effect), is counted without the aid of any instrument. In both methods, median effective concentrations ($EC_{50}$ values) were computed based on the results over a range of dosed toxicant concentrations. It showed that TTBTC was as sensitive as the standard 48-hour acute bioassay and CAUST. TTBTC and CAUST were much more sensitive than the I-hour I.Q. test and 30-minute Microtox. This study indicates that TTBTC is an easier and more rapid toxicity test than the standard 48-hour acute bioassay and even CAUST.

• 한국환경보건학회지
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• 제19권2호
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• pp.61-68
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• 1993

This study aimed at evaluating the preventive effect of Glycyrrhizae Radix and Glycine Semen Extract (GGE) against NAC intoxication. NAC is widely used pesticide in many countries and derivative of carbamats and GGE is well-known antidote to some kinds of toxicants which was referenced from oriental medicine text. The results obtained were as follows: 1) After injecting NAC (100,140 mg/kg), determined Ch.E activities decrease 44.77~50.86% for all experimental groups at one hour after exposure, and were gradually recovered in the course of time. 2) In toxicity test of GGE, there were no sign of death or poisoning up to 5000 mg/kg of GGE for p.o. in mice. From this, we suggest that the LD$_{50}$ of GGE would be above 5000 mg/kg. 3) The Ch.E activity in control group was 471.43 $\pm$ 4.85 luff, group I was 215.27 $\pm$ 23.13 IU/l, group II and group III were 304.03 $\pm$ 9.03 IU/l, 433.81 $\pm$ 21.73 IU/l, respectively. Compare to the control group with experimental group I, remarkable difference revealed (p< 0.01), but the Ch.E activities of group II and III were similar to those of control group. This is indicate that GGE possess a potent activity of recovering Ch.E. GGE had a very remarkable preventive effect on NAC toxicity, and it was able to know that Ch.E activity dramatically increased according to GGE dosage increasing. 4) When GGE and NAC were administered by p.o. simultaneously, LD$_{50}$ and confidence intervals of each group were as follows: the control group: 270 mg/kg, 234.99~310.23 mg/kg, group I and II (GGE 500 mg/kg, 1000 mg/kg by p.o.): 310 mg/kg, 271.69~353.71mg/kg, and 325 mg/kg, 285.09~370.50 mg/kg, respectively. In the comparison with the control group, the protective index was 1.1 and 1.2, respectively. From the above result, GGE has reactivation effect to decreasing Ch.E activity induced by exposure to NAC. Furthermore, GGE shows a preventive effect on NAC intoxication.

• 한국환경보건학회지
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• 제21권1호
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• pp.68-73
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• 1995

화합물질의 개발사용 및 환경오염 물질의 증가로 인하여 남성수태능력에 영향을 미치는 물질이 증가하고 있는 형편이다. 따라서 신속하고 경제적으로 남성 수태능력 영향물질을 평가하기 위하여 랫드의 고환세포를 이용한 남성 수태능력시험법을 개발하고자 본 시험을 실시하였다. 랫드의 고환 세포로부터 주요한 기능을 가진 Sertoli cell과 Leyding cell을 효소처리, 필터 그리고 percoll gradient과정을 거쳐 각각 분리하였다. 분리된 두 종류의 세포는 32$\circ$C에서 초기 배양한 후 37$\circ$C에서 계속 배양하였다. 본 배양조건에서 두 종류 세포는 양호한 발육을 보였으며 약 2주간의 배양이 가능하였다. Sertoli cell은 3주령의 랫드에서 분리가 잘되었고 Leydig cell은 85.7%의 생존율을 보였다. 이상의 결과와 같이 랫드의 고환세포중 Sertoli cell과 Leyding cell을 분리 배양하였으며, 앞으로 독성물질의 영향을 평가하기 위한 생화학적 및 구조적인 index 설정을 위한 연구가 필요하다고 사료된다.

• Toxicological Research
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• 제20권3호
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• pp.241-250
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• 2004

We previously found that bisphenol A (BPA) caused neurotoxic behavioral alteration. Since disturbance of calcium homeostasis is an implicated contributor in the neurotoxic mechanism of environmental toxicants, we investigated whether BPA alters calcium homeostasis. Unlike other neurotoxic agents which cause increase of intracellular calcium level, BPA decreased $[Ca^{2+}]_i$ dose-dependently in PC12 cells and cortical neuronal cells regardless of the calcium existence in buffer. BPA at greater concentrations than 100 $\mu\textrm{M}$ reduced cell viability significantly in both types of cells. BPA also suppressed L-glutamate (L-type channel activator, 30 mM) and trifluoperazine (calmodulin antagonist, 30 $\mu\textrm{M}$)-induced increase of $[Ca^{2+}]_i$. BPA further lowered caffeine (RYR activator, 100 $\mu\textrm{M}$)-decreased $[Ca^{2+}]_i$, but did not alter dantrolene (RYR inhibitor, 100 $\mu\textrm{M}$), heparin (IP3 inhibitor, 200 units/ml) and xestospongin C (IP3 inhibitor, 5 $\mu\textrm{M}$)-decreased $[Ca^{2+}]_i$. Cell viability was not directly related to intracellular calcium change by bisphenol A that alternation of intracellular calcium may not be a direct causal factor of BPA-induced neuronal cell death.

• Molecular & Cellular Toxicology
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• 제5권1호
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• pp.67-74
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• 2009

Exposures to environmental chemicals that mimic endogenous hormones are proposed for a number of adverse health effects, including infertility, abnormal prenatal and childhood development and above all cancers. In addition, recently miRNA (micro RNA) has been recognized to play an important role in various diseases and in cellular and molecular responses to toxicants. In this study, endocrine disrupting environmental toxicant, nonylphenol (NP) was treated to MCF-7 (Human breast cancer cell) and HepG2 (Human hepatocellular liver carcinoma) cell line at 3 hrs and 48 hrs time point and miRNA analysis using $mirVana^{TM}$ miRNA bioarray was performed and compared with total mRNA microarray data for the same cell line and treatment. Robust data quality was achieved through the use of dye-swap. Analysis of microarray data identifies a total of 20 and 11 miRNA expressions at 3 hrs and 48 hrs exposure to NP in MCF-7 cell line and a total of 14 and 47 miRNA expression at 3 hrs and 48 hrs exposure respectively to NP in HepG2 cell line. Expression profiling of the selected miRNA (let-7c, miR-16, miR-195, miR-200b, miR200c, miR-205, and miR-589) reveals changes in the expression of target genes related to metabolism, immune response, apoptosis, and cell differentiation. The present study can be informative and helpful to understand the role of miRNA in molecular mechanism of chemical toxicity and their influence on hormone dependent disease. Also this study may prove to be a valuable tool for screening potential estrogen mimicking pollutants in the environment.

• Molecular & Cellular Toxicology
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• 제5권2호
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• pp.99-107
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• 2009

Naphthalene is bicyclic aromatic compound that is widely used in various domestic and commercial applications including lavatory scent disks, soil fumigants and moth balls. Exposure to naphthalene results in the development of bronchiolar damage, cataracts and hemolytic anemia in humans and laboratory animals. However, little information is available regarding the mechanism of naphthalene toxicity. We investigated gene expression profiles and potential signature genes in human hepatocellular carcinoma HepG2 cells and human promyelocytic leukemia HL-60 cells after 3 h and 48 h incubation with the IC$_{20}$ and IC$_{50}$ of naphthalene by using 44 k agilent whole human genome oligomicroarray and operon human whole 35 k oligomicroarray, respectively. We identified 616 up-regulated genes and 2,088 down-regulated genes changed by more than 2-fold by naphthalene in HepG2 cells. And in HL-60, we identified 138 up-regulated genes and 182 down-regulated genes changed by more than 2-fold. This study identified several interesting targets and functions in relation to naphthalene-induced toxicity through a gene ontology analysis method. Apoptosis and cell cycle related genes are more commonly expressed than other functional genes in both cell lines. In summary, the use of in vitro models with global expression profiling emerges as a relevant approach toward the identification of biomarkers associated with toxicity after exposure to a variety of environmental toxicants.