• Environmental Mutagens and Carcinogens
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• 제21권2호
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• pp.89-94
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• 2001

Recently, single cell gel electrophoresis, also known as comet assay, is widely used for the detection and measurement of DNA strand breaks in vitro and in vivo in many toxicological fields such as radiation exposure, human monitoring and toxicity evaluation. As well defined, comet assay is a sensitive, rapid and visual method for the detection of DNA strand breaks in individual cells. Briefly, a small number of damaged cells suspended in a thin agarose gel on a microscope slide were lysed, unwinded, electrophoresed, and stained with a fluorescent DNA binding dye. The electric current pulled the charged DNA from the nucleus such that relaxed and broken DNA fragments migrated further. The resulting images which were subsequently named for their appearance as comets, were measured to determine the extent of DNA damages. However, some variations could be occurred in procedures, laboratories's conditions and kind of cells used. Hence, to overcome and to harmonize these matters in comet assay, International Workshop on Genotoxicity Test Procedure (IWGTP) was held with several topics including comet assay at Washington D.C. on March, 1999. In spite of some consensus in procedures and conditions in IWGTP, there are some problems still remained to be solved. In this respect, we attempted to set the practical optimal conditions in the experimental procedures such as lysis, unwinding, electrophoresis and neutralization conditions and so on. First of all, we determined optimal lysis and unwinding time by using 150 $\mu$M methyl methanesulfonate (MMS) which is usually used concentration. And then, we determined optimal positive control concentrations of benzo(a)pyrene (BaP) and MMS in the presence and absence of S9 metabolic activation system, respectively.

• Biomolecules & Therapeutics
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• 제13권2호
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• pp.65-77
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• 2005

Present article reviews about clinical pharmacology of mycophenolic acid (MPA), the active form of mycophenolate mofetil (MMF), as widely used component of immunosuppressive regimens in the organ transplantation field. MMF, used alone or concomitantly with cyclosporine or tacrolimus, has approved in reducing the incidence of acute rejection and has gained widespread use in solid organ such as kidney, heart and liver transplantation. The application of MPA and development of MMF has shown a considerable impact on immunosuppressive therapy for organ transplantation as a new immunosuppressive agent with different mechanism of action from other drugs after early 1990s. In particular aspect, use of MMF, a morpholinoethyl ester of MPA, represented a significant advance in the prevention of organ allograft rejection as well as allograft and patient survival. In considering MMF clinical data, it is important to note that there is a strong correlation between high MPA area under curve(AUC) values and a low probability of acute allograft rejection. Individual trials have shown that MMF is generally well tolerated and revealed that MMF decreased the relative risk of developing chronic allograft rejection compared with azathioprine. Recent clinical investigations suggested that improved effectiveness and tolerability will results from the incorporation of MPA therapeutic drug monitoring into routine clinical practice, providing effective MMF dose individualization in renal and heart transplant patients. Therefore, MMF has a selective immunosuppressive effect with minimal toxicity and has shown to be more effective that other agents as next step of immunosuppressive agents and regimens that deliver effective graft protection and immunosuppression along with a more favorable side effect.

• Biomedical Science Letters
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• 제9권4호
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• pp.195-201
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• 2003

Aromatic hydrocarbons are of major concern among genotoxic chemicals due to their toxicity and persistence. Some microorganisms can utilize aromatic hydrocarbons as carbon and energy sources by inducing expression of catabolic operon(s). The XylR regulatory protein activates transcription of the catabolic enzymes to degrade BTEX (benzene, toluene, ethylbenzene, and xylene) from its cognate promoters, Pu and Ps upon exposure of the cells to the aromatic hydrocarbons. The activity of XylR on the promoters was previously monitored using luciferase luc reporter system. The xylR, its promoter Pr and the promoter Po for the phenolic compound catabolic operon were introduced upstream of firefly luciferase luc in the pGL3b vector to generate about 7.1 kb of pXRBTEX. Here E. coli harboring the plasmid was freeze-dried under various conditions to fin,d optimal conditions for storage and transport. The cell viability and luciferase activity were maintained better, when the cells were freeze-dried at -7$0^{\circ}C$ in the addition of the 10% skim milk or 12% sucrose. However, coaddition of protectants such as 10% skim milk plus 10% glucose or 12% sucrose plus 10% glucose, resulted in much better viability and bioluminescence activity compared with the effect of single addition of each protectant. In addition, it was shown that the freeze-dried cells maintained almost intact bioluminescent activities and cell viability for at least 1 week after freeze-drying. This work demonstrated that the properly freeze-dried recombinant bacterial cells could be utilized as a whole-cell biosensor for simple and rapid monitoring of BTEX in the environment.

• Journal of Preventive Medicine and Public Health
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• 제41권5호
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• pp.345-354
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• 2008

Objectives : Our objective is to review and summarize the previous studies on the health effects of exposure to oil spills in order to make suggestions for mid- and long-term study plans regarding the health effects of the Hebei Spirit oil spill occured in Korea. Methods : We searched PubMed to systemically retrieve reports on the human health effects related to oil spill accidents. The papers' reference lists and reviews on the topic were searched as well. Results : We found 24 articles that examined seven oil spill accidents worldwide over the period from 1989 to August 2008, including the Exxon Valdes, Braer, Sea Empress, Erika, Nakhodka, Prestige and Tasman Spirit oil spills. Most of the studies applied cross-sectional and short-term follow-up study designs. The exposure level was measured by assessing the place of residence, using a questionnaire and environmental and personal monitoring. Studies on the acute or immediate health effects mainly focused on the subjective physical symptoms related to clean-up work or residential exposure. Late or mid-term follow-up studies were performed to investigate a range of health effects such as pulmonary function and endocrine, immunologic and genetic toxicity. The economic and social impact of the accidents resulted in the socio-psychological exposure and the psychosocial health effects. Conclusions : Studies of the health effects of exposure to oil spills should consider a range of health outcomes, including the physical and psychological effects, and the studies should be extended for a considerable period of time to study the long-term chronic health effects.

• The Korean Journal of Nuclear Medicine
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• 제14권2호
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• pp.10-17
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• 1980

Gentamicin is useful to the Gram negative bacterial infection, but its nephrotoxicity is a serious problem and the incidence is probably increasing. The toxicity of gentamicin to the kidney is site-specific to the proximal tubule. In this study, we measured daily peak and trough level of gentamicin, serum creatinine, serum $Beta_2$-microglobulin and 24-hr urine $Beta_2$-microglobulin in 10 gentamicin treated patients. All the patients had their peak levels of gentamicin in the safe therapeutic range, and their trough level showed no evidence of gentamicin accumulation. There was no patient who showed his daily serum creatinine and $Beta_2$-microglobulin rise significantly. But 24-hour urine $Beta_2$-microglobulin showed significant rise from basal level (mean $5.8{\pm}1.62{\times}$) on the 5 th day of gentamicin treatment. Thus, serial monitoring of proximal tubular function with urinary $Beta_2$-microglobulin excretion has potential value in the assessment of insults of gentamicin to this site. But clinical significance of raised urinary $Beta_2$-microglobulin excretion in relation to the serum creatinine should be further studied.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 한국환경독성학회 2003년도 춘계학술대회
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• pp.187-187
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• 2003

Methylmercury (MeHg), one of the heavy metal compounds, can cause severe damage to the central nervous system in humans. Many reports have shown that MeHg is poisonous to human body through contaminated foods and has released into the environment. Despite many studies on the pathogenesis of MeHg-induced central neuropathy, no useful mechanism of toxicity has been established so far. In this study, two methods, cDNA Microarray and SSH, were performed to assess the expression profile against MeHg and to identify differentially expressed genes by MeHg in neuroblastoma cell line. TwinChip Human-8K (Digital Genomics) was used with total RNA from SH-SY5Y (human neuroblastoma cell line) treated with solvent (DMSO) and 6.25 uM (IC50) MeHg. And we performed forward and reverse SSH method on mRNA derived from SH-SY5Y treated with DMSO and MeHg (6.25 uM). Differentially expressed cDNA clones were sequenced and were screened by dot blot and ribonuclease protection assay to confirm that individual clones indeed represent differentially expressed genes. These sequences were identified by BLAST homology search to known genes or expressed sequence tags (ESTs). Analysis of these sequences may provide an insight into the biological effects of MeHg in the pathogenesis of neurodegenerative disease and a possibility to develop more efficient and exact monitoring system of heavy metals as environmental pollutants.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 한국환경독성학회 2003년도 춘계학술대회
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• pp.150-151
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• 2003

Benzoyl peroxide is a high production volume chemical, which was produced about 1,375 tons/year in Korea as of 2001 survey. Most of them are used as initiators in polymerization, catalysts in the plastics industry, bleaching agents for flour and medication for acne vulgaris. The substance is one of the sever chemicals of which human and environmental risks are being assessed by National Institute of Environmental Research under the frame of OECD SIDS Program. It has a melting point of 104-106 $^{\circ}C$ and has solubility of 9.1 mg/1 in water at 25 $^{\circ}C$. The substance was readily biodegradable (83 % after 21days) and had toxic effects to aquatic organisms. The range of 72 hr-EbC50 (biomass) for algae was 0.07-0.44 mg/1 and 48 hr-EC50 for daphnia was 0.07-2.91 mg/1. The LC50 of acute toxicity to fish was 0.24-2.0 mg/1. Although the toxic effects of benzoyl peroxide to aquatic organisms were investigated, environmental monitoring data were not studied. In this study, distribution of the chemical among multimedia environment was estimated using EQC model based on the physical-chemical properties to evaluate the risk of benzoyl peroxide in environment. In level I, II calculation the chemical was distributed to soil (68.3 %) and water (28.7 %). In level III calculation it was primarily distributed to soil (99.9 %) and overall residence time of 3.4 years was estimated. Benzoyl peroxide could be persistent in environment.

• Analytical Science and Technology
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• 제11권4호
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• pp.243-247
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• 1998

Cisplatin is a platinum-containing antitumor agent with nephrotoxic and neurotoxic side effects. An analytical method for measuring cisplatin in plasma by FAAS was developed, which is rapid, simple and need no sample preparation. The linearity test of calibration curve in the range of 20~1000 ng/mL showed good correlation coefficient of r=0.999. The result of accuracy test appeared to be relative standard deviation of < 5.0% at concentration range from 50 to 1000 ng/mL. When $200{\mu}L$ of plasma was used, detection limit was 10 ng/mL. Therefore, it can be applied for the monitoring in plasma for optimal condition of treatment and reduce of toxicity.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2467-2471
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• 2012

Introduction: Although bleomycin/etoposide/cisplatinum (BEP) chemotherapy is established as the standard treatment for germ cell tumours, it requires significant experience in administration and toxicity management to maintain optimal dose intensity. A retrospective review of 30 patients was conducted at UKMMC to study treatment outcomes. Methods & Materials: Patients with GCTs and treated with at least two cycles of BEP chemotherapy between January 2003 and Oct 2009 were eligible for this study. Patients received 4-6 cycles of bleomycin 30,000IU IV D1, D8 & D15 and either etoposide $100mg/m^2$ IV D1-D5 and cisplatin $20mg/m^2$ IV D1-D5 (5 day BEP regimen) or etoposide $165mg/m^2$ D1-D3 and cisplatin $50mg/m^2$ D1-3 (3 day BEP regimen) every three weeks per cycle. All patients received prophylactic granulocyte colony-stimulating factor (GCSF) from days 6 to 10 of each cycle. The overall response rates, 2 year progression-free survival and overall survival of the whole cohort were assessed. Results: Thirty patients fulfilled the inclusion criteria. Non-seminomatous GCTs comprised 93.3% of cases and gonadal and mediastinal primary sites were the most common. Sixty percent were classified as IGCCCG poor risk disease. Median follow-up was 26.6 months. The overall response rate (CR+PR) was 70%. The two year PFS and OS were 70% and 66%. There was a significant difference in terms of the overall response rate (85% vs 40%, p = 0.03) and in PFS (94.7% vs 50%, p = 0.003) between gonadal and extragonadal primary sites. Conclusion: It is possible to achieve outcomes similar to those in international clinical trials with close monitoring and good supportive care of patients undergoing BEP chemotherapy. There is a strong argument for patients with IGCCCG poor prognosis disease to be treated in specialist tertiary centres to optimize treatment outcomes.

• Safety and Health at Work
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• 제2권1호
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• pp.39-51
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• 2011

Objectives: This study was designed to evaluate exposure levels of various chemicals used in wafer fabrication product lines in the semiconductor industry where work-related leukemia has occurred. Methods: The research focused on 9 representative wafer fabrication bays among a total of 25 bays in a semiconductor product line. We monitored the chemical substances categorized as human carcinogens with respect to leukemia as well as harmful chemicals used in the bays and substances with hematologic and reproductive toxicities to evaluate the overall health effect for semiconductor industry workers. With respect to monitoring, active and passive sampling techniques were introduced. Eight-hour long-term and 15-minute short-term sampling was conducted for the area as well as on personal samples. Results: The results of the measurements for each substance showed that benzene, toluene, xylene, n-butyl acetate, 2-methoxy-ethanol, 2-heptanone, ethylene glycol, sulfuric acid, and phosphoric acid were non-detectable (ND) in all samples. Arsine was either "ND" or it existed only in trace form in the bay air. The maximum exposure concentration of fluorides was approximately 0.17% of the Korea occupational exposure limits, with hydrofluoric acid at about 0.2%, hydrochloric acid 0.06%, nitric acid 0.05%, isopropyl alcohol 0.4%, and phosphine at about 2%. The maximum exposure concentration of propylene glycol monomethyl ether acetate (PGMEA) was 0.0870 ppm, representing only 0.1% or less than the American Industrial Hygiene Association recommended standard (100 ppm). Conclusion: Benzene, a known human carcinogen for leukemia, and arsine, a hematologic toxin, were not detected in wafer fabrication sites in this study. Among reproductive toxic substances, n-butyl acetate was not detected, but fluorides and PGMEA existed in small amounts in the air. This investigation was focused on the air-borne chemical concentrations only in regular working conditions. Unconditional exposures during spills and/or maintenance tasks and by-product chemicals were not included. Supplementary studies might be required.