• Environmental Analysis Health and Toxicology
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• v.20 no.4 s.51
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• pp.365-374
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• 2005

Ambient air particulate matters are classified into two distinct modes in sire distribution, namely the coarse and fine particles. Correlation between high particulate concentration and adverse effect on human populations has long been recognized. However, the toxicology of these adverse efforts has not been clarified. We investigated the genotoxic effect of PM 2.5 collected from urban area in Seoul by comet assay (A549 cells), CBMN assay (CHO-K1 cells) and EROD-microbioassay (H4IIE cells). Results from in vitro micronucleus assay and comet assay showed that PM 2.5 samples collected from traffic area, residential area and indoor air induced chromosomal damage and DNA breakage in a non-cytotoxic dose. The complex mixture effect of these PM 2.5 extracts was quantified by EROD-microbioassay in terms of its bio-TEQ (biologiral -TCDD equivalent concentration) which was 70.87$\pm$28.07, 93.55$\pm$21.80 and 14.31 $\pm$ 1.10 ng/g-PM 2.5 in traffic area, residental area and indoor air samples, respectively. Conclusively, we suggested that PM 2.5 collected from traffic area and residential area contains CYPIA inducer and genotoxic materials.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6955-6960
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• 2014

Background: The cytokinesis-block micronucleus (CBMN) assay is a standard cytogenetic tool employed to evaluate chromosomal damage subsequent to pesticide exposure. Objectives: To evaluate the pooled levels of total micronuclei (MN) and binucleated cells with micronuclei (MNC) in 1000 binucleated lymphocytes among population occupationally exposed to pesticides and further determine the more sensitive biomarker of CBMN. Materials and Methods: A meta-analysis on the pooled levels of MN and MNC in binucleated lymphocytes among occupationally pesticide-exposed populations was conducted using STATA 10.0 software and Review Manager 5.0.24 in this study. Results: We found significant differences in frequencies of MN and MNC in 1000 binucleated lymphocytes between pesticide-exposed groups and controls, and the summary estimates of weighted mean difference were 6.82 [95% confidence interval (95% CI): 4.86-8.78] and 5.08 (95% CI: 2.93-7.23), respectively. However, when we conducted sensitivity analyses further, only the MN remained statistically different, but not the MNC, the summary estimates of weight mean difference were 2.86 (95% CI: 2.51-3.21) and 0.50 (95% CI: -0.16-1.17), respectively. We also observed pesticide-exposed subjects had significantly higher MN frequencies than controls among smokers and nonsmokers, male and female populations, and American, Asian and European countries in stratified analyses. Conclusions: The frequency of MN in peripheral blood lymphocytes might be a more sensitive indicator of early genetic effects than MNC using the CBMN assay for occupationally pesticide-exposed populations.

• Nuclear Engineering and Technology
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• v.38 no.3
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• pp.231-238
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• 2006

Whole-body exposure to high-dose radiation causes injury involving multiple organs that depends on their sensitivity to radiation. This acute radiation syndrome (ARS) is caused by a brief exposure of a major part of the body to radiation at a relatively high dose rate. ARS is characterized by an initial prodromal stage, a latent symptom-free period, a critical or manifestation phase that usually takes one of four forms (three forms): hematologic, gastrointestinal, or cardiovascular and neurological (neurovascular), depending upon the exposure dose, and a recovery phase or death. One of the most important factors in treating victims exposed to radiation is the estimation of the exposure dose. When high-dose exposure is considered, initial dose estimation must be performed in order to make strategy decisions for treatment as soon as possible. Dose estimation can be based on onset and severity of prodromal symptoms, decline in absolute lymphocyte count post exposure, and chromosomal analysis of peripheral blood lymphocytes. Moreover, dose assessment on the basis of calculation from reconstruction of the radiation event may be required. Experience of a criticality accident occurring in 1999 at Tokai-mura, Japan, showed that ARS led to multiple organ failure (MOF). This article will review ARS and discuss the possible mechanisms of MOF developing from ARS.

• The Journal of Internal Korean Medicine
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• v.21 no.4
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• pp.535-542
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• 2000

The water extracts of Samul-tang(SMT) has been used for treatment of ischemic brain damage in Oriental traditional medicine. However, little is known about the mechanism by which the water extracts of SMT rescues brain cells from ischemic damages. To elucidate the protective mechanism on ischemic induced cytotoxicity, I investigate the regulation of LPS and PMA induced iNOS expression in C6 glial cells. LPS and PMA treatment for 72 h in C6 glial cells markedly induce nitric oxide(NO), but treatment of the cells with the water extracts of SMT decrease. dose dependently nitrite formation. In addition, LPS and PMA treatment for 72 h induce severe cell death and LDH release in C6 glial cells. However treatment of the cells with the water extracts of SMT dose not induce significant changes compare to control cells. Furthermore, the protective effects of the water extracts of SMT is mimicked by treatment of $N^{G}MMA$, a specific inhibitor of NOS. LPS and PMA induced iNOS activation in C6 glial cells cause chromosomal condensation and fragmentation of nuclei by caspase activation. The treatment of the cells with the water extracts of SMT may suppress apoptosis via caspase inhibition by regulation of iNOS expression. Taken together, I suggest that the protective effects of the water extracts of SMT against ischemic brain damages may be mediated by regulation of iNOS during ischemic condition.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5257-5261
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• 2013

The micronucleus frequency (MNF) in peripheral blood lymphocytes (PBL) is a biomarker of chromosomal damage and genome instability in human populations.The relationship of micronucleus frequency with prognosis of patients with acute leukemia is not clear. We therefore investigated MNF in mitogen-activated peripheral blood lymphocytes from patients with hematologic diseases and solid tumours. Patients included 50 with acute leukemia, 49 diagnosed with myelodysplastic syndrome (MDS), 54 with benign blood diseases, and 45 with solid tumours, examined with 50 healthy controls. The mean MNF was significantly higher in cases of hematologic diseases and solid tumor patients than in healthy controls (P<0.001). There was no evident difference between MNF in the acute leukemia ($7.15{\pm}2.18$) and solid tumor groups ($7.11{\pm}1.47$), but both were higher than in the MDS group ($5.12{\pm}1.29$) and benign blood diseases group ($3.08{\pm}1.08$). Taking 7.15‰, the average MNF of the acute leukemia group as standard, and dividing 50 cases of acute leukemia patients into high MNF group ($MNF{\geq}7.15$‰) and low MNF group (MNF<7.15‰). The overall response (complete remission + partial remission) rates of the low MNF group were significantly higher than in the high MNF group (P=0.001). The high MNF group further showed lower overall survival rates than the low MNF group. MNF expression and progression-free survival seemed to have a opposite relationship, with a correlation coefficient of -0.702. These data indicate that MNF in peripheral blood lymphocytes is important for evaluation of prognosis of acute leukemia patients, and it can reflect progression of disease to a certain degree.

• Molecular & Cellular Toxicology
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• v.2 no.3
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• pp.151-158
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• 2006

Khal was a synthetic congener of halocidin, a heterodimeric peptide consisting of 19 and 15 amino acid residues detected in Halocynthia aurantium. This compound was considered a candidate for the development of a novel peptide antibiotic. The genotoxicity of Khal was subjected to high throughput toxicity screening (HTTS) because they revealed strong antibacterial effects. Mouse lymphoma thymidine kinase ($tk^{+/-}$) gene assay (MOLY), single cell gel electrophoresis (Comet) assay and chromosomal aberration assay in mammalian cells and Ames reverse mutation assay in bacterial system were used as simplified, inexpensive, short-term in vitro screening tests in our laboratory. These compounds are not mutagenic in S. typhimurium TA98 and TA100 strains both in the presence and absence of metabolic activation. Before performing the comet assay, $IC_{20}$ of Khal was determined the concentration of $25.51\;{\mu}/mL\;and\;21.99\;{\mu}g/mL$ with and without S-9, respectively. In the comet assay, Khal was not induced DNA damage in mouse lymphoma cell line. Also, the mutation frequencies in the Khal-treated cultures were similar to the vehicle controls. It is suggests that Khal is non-mutagenic in MOLY assay. And no clastogenicity was observed in Khal-treated Chinese hamster lung cells. The results of this battery of assays indicate that Khal has no genotoxic potential in bacterial or mammalian cell systems. Therefore, we suggest that Khal, as the optimal candidates with both no genotoxic potential and antibacterial effects must be chosen.

• Biomolecules & Therapeutics
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• v.4 no.3
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• pp.239-243
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• 1996

DW-116 {(1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-1-piperazinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid hydrochloride) is a new quinolone antibiotic with a broad antibacterial spectrum against G(+) and G(-) bacteria. DW-116 was evaluated for the appearance of micronucleus in polychromatic erythrocytes (PCEs) of mouse bone marrow cells after intraperitoneal and oral single administration. We prepared the bone marrow cells at 30hr after drug administration and they were used for measuring PCE with micronucleus. The results showed there was no statistically significant increase in the numbers of PCEs with micronucleus in all DW-116 administered groups compared with a negative control group. The results also showed that the ratio of normochromatic erythrocytes(NCEs) to PCEs of all DW-116 administered groups was not significantly different from that of a negative control group. These results suggested that DW-116 may not cause any chromosomal damage and it has no in vivo mutagenic potential under these experimental conditions.

• Radiation Oncology Journal
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• v.18 no.2
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• pp.138-149
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• 2000

Purpose : It was studied that the relationship between radiation dose, dose rate and the frequency of chromosomal aberrations in peripheral lymphocytes. Methods and Materials : Peripheral lymphocytes were irradiated in vitro with 6 MeV X-ray at dose ranges from 50 cGy to 800 cGy. The variations of the frequency of chromosomal aberrations were observed according to different radiation dose rate from 20 cGy/min to 400 cGy/min at constant total dose of 400 cGy which it was considered as factor to correct biological radiation dose measurement. Results : The yields of lymphocytes with chromosomal aberrations (dicentric chromosome, ring chromosome, acentric fragment pairs) are 0% at 50 cGy, 9% at 100 cGy, 20% at 200 cGy, 27% at 300 cGy, 55% at 400 cGy, 88% at 600 cGy, and 100% at 800 cGy. The value of Ydr is 0.000 at 50 cGy, 0.093 at 100 cGy, 0.200 at 200 cGy, 0.354 at 300 cGy, 0.612 at 400 cGy, 2.040 at 600 cGy, and 2.846 at 800 cGy. The relationship between radiation (D) and the frequency of dicentrlc chromosomes and ring Chromosomes (Ydr) can be expressed as Ydr=0.188${\times}$10$^{-2}$ D/Gy+0.422${\times}$10$^{-4}$/Gy$^{2}$${\times}$D$^{2}$ The Value of Qdr is 0.000 at 50 cGy, 1.000 at 100 cGy, 1.000 at 200 cGy, 1.333 at 300 cGy, 1.118 at 400 cGy, 2.318 at 600 cGy, and 2.846 at 800 cGy. When 400 cGy is irradiated with different dose rate each of 20, 40, 60, 80, 100, 160, 240, 320, and 400 cGy/min, Ydr is each of 0.982, 0.837, 0.860, 0.732, 0.763, 0.966, 0.909, 1.006, and 0.806, and Qdr is each of 1.839, 1.555, 1.654, 1.333, 1.381, 1.750, 1.6000, 1.710, and 1.318. Conclusion : There are not the significant variations of Ydr and Qdr values according to different dose rate. And so radiation damage is influenced by total exposed radiation doses and is influenced least of all by different dose rate when it is acute single exposure.

• Animal Bioscience
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• v.34 no.4
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• pp.546-557
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• 2021

Objective: If fertilization does not occur within a specific period, the quality of unfertilized oocytes in the oviduct (in vivo aging) or in culture (in vitro aging) will deteriorate over time. Icariin (ICA), found in all species of Epimedium herbs, has strong antioxidant activity, and is thought to exert anti-aging effects in vitro. We asked whether ICA protects oocytes against age-related changes in vitro. Methods: We analyzed the reactive oxygen species (ROS) levels and expression of antioxidant, maternal, and estrogen receptor genes, and along with spindle morphology, and the developmental competence and quality of embryos in the presence and absence of ICA. Results: Treatment with 5 μM ICA (ICA-5) led to a significant reduction in ROS activity, but increased mRNA expression of glutathione and antioxidant genes (superoxide dismutase 1 [SOD1], SOD2, peroxiredoxin 5, and nuclear factor erythroid 2-like 2), during aging in vitro. In addition, ICA-5 prevented defects in spindle formation and chromosomal alignment, and increased mRNA expression of cytoplasmic maturation factor genes (bone morphogenetic protein 15, cyclin B1, MOS proto-oncogene, serine/threonine kinase, and growth differentiation factor-9). It also prevented apoptosis, increased mRNA expression of antiapoptotic genes (BCL2-like 1 and baculoviral IAP repeat-containing 5), and reduced mRNA expression of pro-apoptotic genes (BCL2 antagonist/killer 1 and activation of caspase-3). Although the maturation and cleavage rates were similar in all groups, the total cell number per blastocyst and the percentage of apoptotic cells at the blastocyst stage were higher and lower, respectively, in the control and ICA-5 groups than in the aging group. Conclusion: ICA protects oocytes against damage during aging in vitro; therefore, it can be used to improve assisted reproductive technologies.

• Biomolecules & Therapeutics
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• v.5 no.3
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• pp.278-283
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• 1997

DW-166HC ($^{166}$ Holmium ($^{166}$ Ho)-Chitosan complex) is a new radiopharmaceutic anticancer agent with a broad anti-tumoriginec spectrum, especially against human fepatic cancer. DW-166HC was evaluated for the appearance of micronucleus in polychromatic erythrocytes (PCEs) of mouse bone marrow cells after subcutaneous and intravenous single administration. Bone marrow cells were prepared at 24 hr and 48 hr after DW-166HC-I ($^{165}$ Ho-Chitosan complex cold compound) administration and at 24 hr, 72 hr and 2 weeks after DW-166HC ($^{166}$ Ho-Chitosan complex : hot compound) administration. The results showed there was no statistically significant increase of the numbers of PCEs with micronucleus in all DW-166HC-I administered groups compared with a negative control group but there was statistically significant increase of the numbers of PCEs with micronucleus at 24 hr and 72 hr in all DW-166HC administered groups, which was recovered after 2 weeks from the drug administration. The results also showed the ratio of normochromatic erythrocytes (NCEs) to PCEs of all DW-166HC-I administered groups was not significantly different from that of a negative control group but there was significant difference this ratio at 24hr and 72 hr in all DW-166HC administered groups compared with that of negative group, which was also recovered after two weeks from the drug administration. These results suggested that DW-166HC-I may not cause any chromosomal damage but DW-166HC has in vivo mutagenic potential because of its radioactivity.