1.Combined approaches using adverse outcome pathways and big data to find potential diseases associated with humidifier disinfectant.
Jong Han LEEM ; Kyu Hyuck CHUNG
Environmental Health and Toxicology 2017;32(1):e2017003-
According to previous survey, about two million of people were expected to suffer from toxic effects due to humidifier disinfectant (HD), regardless of healing or not. Extremely small group are recognized as HDs’ victims. Up to now, previous research tried to focus on interstitial fibrosis on terminal bronchiole because it is specific finding, compared with other diseases. To figure out overall effects from HDs, we recommend adverse outcome pathways (AOPs) as new approach. Reactive oxygen species (ROS) generation, decreased T-cell and pro-inflammatory cytokine release from macrophage could be key events between the exposure to HDs and diseases. ROS generation, decreased cell and pro-inflammatory cytokine release from macrophage could be cause of interstitial fibrosis, pneumonia and many other diseases such as asthma, allergic rhinitis, allergic dermatitis, fetal death, premature baby, autoimmune disease, hepatic toxicity, renal toxicity, cancer, and so on. We predict potential disease candidate by AOPs. We can validate the real risk of the adverse outcome by epidemiologic and toxicologic study using big data such as National Health Insurance data and AOPs knowledge base. Application of these kinds of new methods can find the potential disease list from the exposure to HD.
Asthma
;
Autoimmune Diseases
;
Bronchioles
;
Dermatitis
;
Fetal Death
;
Fibrosis
;
Humidifiers*
;
Knowledge Bases
;
Macrophages
;
National Health Programs
;
Pneumonia
;
Reactive Oxygen Species
;
Rhinitis, Allergic
;
T-Lymphocytes
2.A review of current studies on cellular and molecular mechanisms underlying pulmonary fibrosis induced by chemicals.
Ha Ryong KIM ; Da Young SHIN ; Kyu Hyuck CHUNG
Environmental Health and Toxicology 2018;33(3):e2018014-
Several studies showed that the inflammatory and fibrotic responses induced by polyhexamethylene guanidine phosphate (PHMG-p) were similar to those observed for idiopathic pulmonary fibrosis in South Korea in 2011. “Omic” technologies can be used to understand the mechanisms underlying chemical-induced diseases. Studies to determine the toxicity of chemicals may facilitate understanding of the mechanisms underlying the development of pulmonary fibrosis at a molecular level; thus, such studies may provide information about the toxic characteristics of various substances. In this review, we have outlined the cellular and molecular mechanisms underlying idiopathic pulmonary fibrosis and described pulmonary fibrosis induced by various chemicals, including bleomycin, paraquat, and PHMG-p, based on the results of studies performed to date.
Bleomycin
;
Epithelial Cells
;
Guanidine
;
Idiopathic Pulmonary Fibrosis
;
Korea
;
MicroRNAs
;
Paraquat
;
Pulmonary Fibrosis*
3.Combined approaches using adverse outcome pathways and big data to find potential diseasesassociated with humidifier disinfectant
Jong Han LEEM ; Kyu Hyuck CHUNG
Environmental Health and Toxicology 2017;32(1):2017003-
According to previous survey, about two million of people were expected to suffer from toxic effects due to humidifier disinfectant (HD), regardless of healing or not. Extremely small group are recognized as HDs’ victims. Up to now, previous research tried to focus on interstitial fibrosis on terminal bronchiole because it is specific finding, compared with other diseases. To figure out overall effects from HDs, we recommend adverse outcome pathways (AOPs) as new approach. Reactive oxygen species (ROS) generation, decreased T-cell and pro-inflammatory cytokine release from macrophage could be key events between the exposure to HDs and diseases. ROS generation, decreased cell and pro-inflammatory cytokine release from macrophage could be cause of interstitial fibrosis, pneumonia and many other diseases such as asthma, allergic rhinitis, allergic dermatitis, fetal death, premature baby, autoimmune disease, hepatic toxicity, renal toxicity, cancer, and so on. We predict potential disease candidate by AOPs. We can validate the real risk of the adverse outcome by epidemiologic and toxicologic study using big data such as National Health Insurance data and AOPs knowledge base. Application of these kinds of new methods can find the potential disease list from the exposure to HD.
Asthma
;
Autoimmune Diseases
;
Bronchioles
;
Dermatitis
;
Fetal Death
;
Fibrosis
;
Humidifiers
;
Knowledge Bases
;
Macrophages
;
National Health Programs
;
Pneumonia
;
Reactive Oxygen Species
;
Rhinitis, Allergic
;
T-Lymphocytes
4.A review of current studies on cellular and molecular mechanisms underlying pulmonary fibrosis induced by chemicals
Ha Ryong KIM ; Da Young SHIN ; Kyu Hyuck CHUNG
Environmental Health and Toxicology 2018;33(3):2018014-
Several studies showed that the inflammatory and fibrotic responses induced by polyhexamethylene guanidine phosphate (PHMG-p) were similar to those observed for idiopathic pulmonary fibrosis in South Korea in 2011. “Omic” technologies can be used to understand the mechanisms underlying chemical-induced diseases. Studies to determine the toxicity of chemicals may facilitate understanding of the mechanisms underlying the development of pulmonary fibrosis at a molecular level; thus, such studies may provide information about the toxic characteristics of various substances. In this review, we have outlined the cellular and molecular mechanisms underlying idiopathic pulmonary fibrosis and described pulmonary fibrosis induced by various chemicals, including bleomycin, paraquat, and PHMG-p, based on the results of studies performed to date.
Bleomycin
;
Epithelial Cells
;
Guanidine
;
Idiopathic Pulmonary Fibrosis
;
Korea
;
MicroRNAs
;
Paraquat
;
Pulmonary Fibrosis
5.Clinical Utility of Magnetic Resonance Angiography.
Se Hyuck PARK ; Bong Sub CHUNG ; Whan EOH ; Kyu Ho LEE ; Kil Woo LEE
Journal of Korean Neurosurgical Society 1992;21(5):567-574
No abstract available.
Imaging, Three-Dimensional
;
Magnetic Resonance Angiography*
6.Appropriate In Vitro Methods for Genotoxicity Testing of Silver Nanoparticles.
Ha Ryong KIM ; Yong Joo PARK ; Da Young SHIN ; Seung Min OH ; Kyu Hyuck CHUNG
Environmental Health and Toxicology 2013;28(1):e2013003-
OBJECTIVES: We investigated the genotoxic effects of 40-59 nm silver nanoparticles (Ag-NPs) by bacterial reverse mutation assay (Ames test), in vitro comet assay and micronucleus (MN) assay. In particular, we directly compared the effect of cytochalasin B (cytoB) and rat liver homogenate (S9 mix) in the formation of MN by Ag-NPs. METHODS: Before testing, we confirmed that Ag-NPs were completely dispersed in the experimental medium by sonication (three times in 1 minute) and filtration (0.2 microm pore size filter), and then we measured their size in a zeta potential analyzer. After that the genotoxicity were measured and especially, S9 mix and with and without cytoB were compared one another in MN assay. RESULTS: Ames test using Salmonella typhimurium TA98, TA100, TA1535 and TA1537 strains revealed that Ag-NPs with or without S9 mix did not display a mutagenic effect. The genotoxicity of Ag-NPs was also evaluated in a mammalian cell system using Chinese hamster ovary cells. The results revealed that Ag-NPs stimulated DNA breakage and MN formation with or without S9 mix in a dose-dependent manner (from 0.01 microg/mL to 10 microg/mL). In particular, MN induction was affected by cytoB. CONCLUSIONS: All of our findings, with the exception of the Ames test results, indicate that Ag-NPs show genotoxic effects in mammalian cell system. In addition, present study suggests the potential error due to use of cytoB in genotoxic test of nanoparticles.
Animals
;
Comet Assay
;
Cricetinae
;
Cricetulus
;
Cytochalasin B
;
DNA
;
Female
;
Filtration
;
Liver
;
Micronucleus Tests
;
Mutagenicity Tests*
;
Nanoparticles*
;
Ovary
;
Rats
;
Salmonella typhimurium
;
Silver*
;
Sonication
7.Evaluation of Carcinoembryonic Antigen and Alpha-Fetoprotein in Neurologic Lesions.
Won Hyuck LEE ; Choong Kyum PARK ; Hae Dong JHO ; Young Rak YOO ; Nam Kyu KIM ; Hwan Yung CHUNG
Journal of Korean Neurosurgical Society 1982;11(4):499-506
Carcinoembryonic antigen(CEA) in blood and CSF was reported to be increased in cases of nervous system neoplasms by some investigators. To evaluate the oncological diagnostic value of CEA in the neurosurgical conditions, this study has been performed on 24 nervous system neoplasms and 8 non-nervous system as well as 49 controls. In addition, alpha-fetoprotein was also measured on the same conditions because of its close oncologic nature and recent diagnostic application on the general surgical conditions. The CEA concentration in blood and CSF were determined by CEA Radioimmunoassay kit, and the alpha-fetoprotein in blood and CSF were determined by GammaDab kit. The result showed that concentration of CEA and alpha-fetoprotein was higher and seemed to diagnostic in Extra-CNS neoplasma. In nerovous system, however, these were the lower than we expected, although were higher than control. Moreever, these levels were not unique on same oncologic condition and rather somewhat variable. From these results, increased concentration of these itself may be considered suggestive of existence of nervous system neoplasm, but it does mean neither degree of malignancy nor its origin.
alpha-Fetoproteins*
;
Carcinoembryonic Antigen*
;
Central Nervous System
;
Humans
;
Nervous System Neoplasms
;
Radioimmunoassay
;
Research Personnel
8.Molecular Cloning and Characterization of the Estrogen Receptor from the Slender Bitterling (Acheilognathus yamatsutae).
Jong Geuk KIM ; Ha Ryong KIM ; Yong Joo PARK ; Kyu Hyuck CHUNG ; Seung Min OH
Environmental Health and Toxicology 2011;26(1):e2011005-
OBJECTIVES: In order to identify the possibility of slender bitterling (SB) (Acheilognathus yamatsutae) being used as a test species for estrogenic endocrine disrupting chemicals (EEDCs), we carried out the cloning and sequence characterization of the estrogen receptor (ER). METHODS: The ER from a slender bitterling was obtained by reverse transcriptase-polymerase chain reaction (RT-PCR), 5'- and 3'-rapid amplification of cDNA ends (5'-RACE and 3'-RACE) and T-vector cloning. The expression of ER mRNA was also analyzed in six tissues (brain, liver, kidney, gill, gonad, and intestines) by real-time PCR. RESULTS: We obtained an ER from the slender bitterling. The SB ER cDNA was 2189 base pairs (bp) in length and contained a 1707 bp open reading frame that encoded 568 amino acid residues. The SB ER amino acid sequence clustered in a monophyletic group with the ERalpha of other fish, and was more closely related to zebrafish ERalpha (88% identity) than to the ERalpha of other fish. The SB ER cDNA was divided into A/B, C, D, E and F domains. The SB ER has conserved important sequences for ER functions, such as the DNA binding domain (D domain), which are consistent with those of other teleosts. CONCLUSIONS: The ER of the slender bitterling could provide basic information in toxicological studies of EEDCs in the slender bitterling.
Amino Acid Sequence
;
Animals
;
Base Pairing
;
Clone Cells
;
Cloning, Molecular
;
Cloning, Organism
;
DNA
;
DNA, Complementary
;
Endocrine Disruptors
;
Estrogen Receptor alpha
;
Estrogens
;
Gills
;
Gonads
;
Kidney
;
Liver
;
Open Reading Frames
;
RNA, Messenger
;
Zebrafish
9.The Role of p53 in Marijuana Smoke Condensates-induced Genotoxicity and Apoptosis.
Ha Ryong KIM ; Bo Hee SON ; Soo Yeun LEE ; Kyu Hyuck CHUNG ; Seung Min OH
Environmental Health and Toxicology 2012;27(1):e2012017-
OBJECTIVES: Marijuana is one of the most frequently abused drug in Korea and its adverse health effects are controversial. p53 is known to be crucial in regulating the DNA damage responses, and adverse effects can occur when it is regulated by marijuana smoke. We evaluated a role of p53 on genotoxic effect and apoptosis in lung cancer cells exposed to marijuana smoke condensates (MSCs). METHODS: The p53-related genotoxicity and apoptosis of MSCs were evaluated using in vitro bioassay, viz., comet assay, cytokinesis-block micronucleus assay and apoptosis assay. We used two cell lines with differential p53 expression (p53-wildtype (WT) H460 and p53-null H1299). RESULTS: MSCs significantly increased DNA breakages and chromosomal changes in p53-WT H460 and p53-null H1299 cells. The genotoxicity induced by MSCs in p53-null H1299 cells showed greater sensitivity than p53-WT H460 cells. Moreover, MSCs showed a significant increase in reactive oxygen species production and apoptosis. The apoptotic responses induced by MSCs were higher in p53-WT H460 cells than in p53-null H1299 cells. Significantly increased mRNA expression or apoptosis related genes, including p53, caspase-3, and Bax/Bcl-2 ratio were observed in the p53-WT H460 cells exposed to MSCs. CONCLUSIONS: These results suggest that MSCs induce DNA/chromosomal damages and apoptosis in human lung cancer cells and p53 plays an important role in the cellular response to MSCs. The present study may have border implications for our understanding of pulmonary diseases.
Apoptosis
;
Biological Assay
;
Cannabis
;
Caspase 3
;
Cell Line
;
Comet Assay
;
DNA
;
DNA Damage
;
Humans
;
Korea
;
Lung Diseases
;
Lung Neoplasms
;
Micronucleus Tests
;
Reactive Oxygen Species
;
RNA, Messenger
;
Smoke
;
Tumor Suppressor Protein p53
10.Comparative evaluation of the mutagenicity and genotoxicity of smoke condensate derived from Korean cigarettes.
Ha Ryong KIM ; Jeong Eun LEE ; Mi Ho JEONG ; Seong Jin CHOI ; Kyuhong LEE ; Kyu Hyuck CHUNG
Environmental Health and Toxicology 2015;30(1):e2015014-
OBJECTIVES: Cigarette smoking is associated with carcinogenesis owing to the mutagenic and genotoxic effects of cigarette smoke. The aim of this study was to evaluate the mutagenic and genotoxic effects of Korean cigarettes using in vitro assays. METHODS: We selected 2 types of cigarettes (TL and TW) as benchmark Korean cigarettes for this study, because they represent the greatest level of nicotine and tar contents among Korean cigarettes. Mutagenic potency was expressed as the number of revertants per μg of cigarette smoke condensate (CSC) total particulate matter whereas genotoxic potency was expressed as a concentration-dependent induction factor. The CSC was prepared by the International Organization for Standardization 3308 smoking method. CHO-K1 cells were used in vitro micronucleus (MNvit) and comet assays. Two strains of Salmonella typhimurium (Salmonella enterica subsp.enterica; TA98 and TA1537) were employed in Ames tests. RESULTS: All CSCs showed mutagenicity in the TA98 and TA1537 strains. In addition, DNA damage and micronuclei formation were observed in the comet and MNvit assays owing to CSC exposure. The CSC from the 3R4F Kentucky reference (3R4F) cigarette produced the most severe mutagenic and genotoxic potencies, followed by the CSC from the TL cigarette, whereas the CSC from the TW cigarette produced the least severe mutagenic and genotoxic potencies. CONCLUSIONS: The results of this study suggest that the mutagenic and genotoxic potencies of the TL and TW cigarettes were weaker than those of the 3R4F cigarette. Further study on standardized concepts of toxic equivalents for cigarettes needs to be conducted for more extensive use of in vitro tests.
Benchmarking
;
Carcinogenesis
;
Comet Assay
;
DNA Damage
;
In Vitro Techniques
;
Kentucky
;
Methods
;
Micronucleus Tests
;
Nicotine
;
Particulate Matter
;
Salmonella typhimurium
;
Smoke*
;
Smoking
;
Tobacco Products*