• Title/Summary/Keyword: Micronucleus.

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Evaluation of General Toxicity and Genotoxicity of the Silkworm Extract Powder

  • Heo, Hyun-Suk;Choi, Jae-Hun;Oh, Jung-Ja;Lee, Woo-Joo;Kim, Seong-Sook;Lee, Do-Hoon;Lee, Hyun-Kul;Song, Si-Whan;Kim, Kap-Ho;Choi, Yang-Kyu;Ryu, Kang-Sun;Kang, Boo-Hyon
    • Toxicological Research
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    • v.29 no.4
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    • pp.263-278
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    • 2013
  • The silkworm extract powder contain 1-deoxynojirimycin (DNJ), a potent ${\alpha}$-glycosidase inhibitor, has therapeutic potency against diabetes mellitus. Therefore, natural products containing DNJ from mulberry leaves and silkworm are consumed as health functional food. The present study was performed to evaluate the safety of the silkworm extract powder, a health food which containing the DNJ. The repeated toxicity studies and gentic toxicity studies of the silkworm extract powder were performed to obtain the data for new functional food approval in MFDS. The safety was evaluated by a single-dose oral toxicity study and a 90 day repeated-dose oral toxicity study in Sprague-Dawley rats. The silkworm extract powder was also evaluated for its mutagenic potential in a battery of genetic toxicity test: in vitro bacterial reverse mutation assay, in vitro chromosomal aberration test, and in vivo mouse bone marrow micronucleus assay. The results of the genetic toxicology assays were negative in all of the assays. The approximate lethal dose in single oral dose toxicity study was considered to be higher than 5000 mg/kg in rats. In the 90 day study, the dose levels were wet at 0, 500, 1000, 2000 mg/kg/day, and 10 animals/sex/dose were treated with oral gavage. The parameters that were monitored were clinical signs, body weights, food and water consumptions, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, organ weights, and histopathological examination. No adverse effects were observed after the 90 day administration of the silkworm extract powder. The No-Observed-Adverse-Effect-Level (NOAEL) of silkworm extract powder in the 90 day study was 2000 mg/kg/day in both sexes, and no target organ was identified.

Cytokinesis-blocked micronuclei in the human peripheral lymphocytes following low dose γ-rays irradiation (저선량의 감마선 피폭된 사람 말초 임파구의 미소핵을 이용한 방사선 생물학적 피폭선량 측정법 연구)

  • Kim, Tae-hwan
    • Korean Journal of Veterinary Research
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    • v.41 no.1
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    • pp.99-104
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    • 2001
  • To determine if micronucleus (MN) assay could be used to predict the absorbed dose of victims after accidental radiation exposure, we carried out to assess the absorbed dose depending on the numerical changes of MN in human peripheral blood lymphocytes after $^{60}Co\;{\gamma}-rays$ exposure in the range of 0.25 to 1 Gy, respectively. The MNs were observed at very low doses, and the numerical changes according to doses. Satisfactory dose-effect calibration curve is observed after low dose irradiation of human lymphocytes in vitro. When plotting on a linear scale against radiation dose, the line of best fit was $Y=(0.02{\pm}0.0009)+(0.033{\pm}0.010)D+(0.012{\pm}0.012)D^2$. The dose-response curve for MN induction immediately after irradiation was linear-quadratic and has a significant relationship between the frequencies of MN and dose. These data show a trend towards increase of the numbers of MN with increasing dose. The number of MN in lymphocytes that were observed in the control group is $0.1610{\pm}0.0093/cell$. Accordingly, MN assay in human peripheral lymphocytes could be a useful in viva model for studying radio-protective drug sensitivity or screening test, microdosimertic indicator and radiation-induced target organ injury. Since MN assay is simple, rapid and reproducible, it will also be a biodosimetric indicator for individual dose assessment after accidental exposure.

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Safety Evaluation of Tobacco Substitute (Herbrette); Inhalation Toxicity, Mutagenicity and Immunotoxicity

  • Song, Kyung Seuk;Park, Kun Ho;Yoo, Gi Yong;Song, Sung-Ok;Kim, Hyun Woo;Kim, Jun Sung;Park, Jin Hong;Eu, Guk Joung;Hua, Jin;Cho, Hyun Sun;Hwang, Soon Kyung;Chang, Seung Hee;Tehrani, Arash Minai;Yu, KyeongNam;Chae, Chan Hee;Cho, Myung Haing
    • Toxicological Research
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    • v.20 no.4
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    • pp.365-374
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    • 2004
  • Inhalation toxicity, mutagenicity, and immunotoxicity tests were performed using a smoke generation system to investigate the safety of Herbrette, a tobacco substitute made with the leaves of Perilla frutescens. ICR mice were exposed to nicotine-free Herbrette smoke with concentrations of 0 (control), 4.08 $\pm$ 1.32 mg/$m^3$ (low dose), 7.72 $\pm$ 2.14 mg/$m^3$ (medium dose) and 12.83 $\pm$ 1.69 mg/$m^3$ (high dose) total particulate matters (TPM) for 4 weeks. When compared to the control group, the body weights, organ weights in the exposed groups did not show any significant differences. However, certain change of several serum chemical data and biochemical parameters were observed, however, the changes were within normal physiological ranges. Moreover, no changes in organ weight, and no gross/microscopic changes were observed between the exposed and control groups. Salmonella typhimurium reverse mutation, in vivo chromosomal aberration and micronucleus assays revealed that Herbrette did not induce mutagenicity. Upon evaluation of peripheral cellular immunity of mice through in vitro lymphocyte proliferation assay, no significant difference was observed in mean stimulation index between the exposed and control groups. Taken together, our results strongly suggest that Herbrette may not cause toxicity on mice under current condition.

Evaluation of DNA Damage and Repair Kinetics in the Earthworm (Eisenia fetida) Exposed to Radiation and Mercury (방사선과 수은에 의해 유도된 Eisenia fetida 체강세포의 DNA 손상 및 수복 평가)

  • Ryu, Tae-Ho;Nili, Mohammad;An, Kwang-Guk;Kim, Jin-Kyu
    • Korean Journal of Environmental Biology
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    • v.29 no.1
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    • pp.68-73
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    • 2011
  • The single cell gel electrophoresis (SCGE) assay is a microelectrophoretic technique for assessments of DNA damage at the level of the individual eukaryotic cell. The SCGE assay, due to its simplicity, sensitivity and need of a few cells, has advantages compared to other genomic damage assays such as sister chromatid exchange, chromosomal aberration and micronucleus test. In this study, investigated were the levels of DNA damage and the repair kinetics in the coelomocytes of Eisenia fetida treated with HgCl2 and ionizing radiation by means of the SCGE assay. For detecting DNA damage and repair in coelomocytes, earthworms (E. fetida) were irradiated with six doses of ${\gamma}$-rays (0, 2.5, 5, 10, 20 and 50 Gy) and in vivo exposed to mercuric chloride at 0, 80 and 160 mg $kg^{-1}$ for 48 hours. Then the Olive tail moments were measured during 0~12 hours after irradiation and 0~72 hours after Hg treatment. The results showed that the more the oxidative stress was induced by mercury and radiation, the longer the repair time was required. Also, the results suggest that the SCGE assay may be used as an important tool for comparison of the sensitivity of different species to oxidative stresses.

Chilodonella hexasticha(Protozoa, Ciliata) from Korean freshwater fish (한국산 담수 어류에 기생하는 Chilodonella hexaticha에 관하여)

  • Ji, Bo-Young;Kim, Ki-Hong;Park, Soo-Il
    • Journal of fish pathology
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    • v.9 no.2
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    • pp.113-118
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    • 1996
  • During a study to document more fully the parasitic ciliates of Korean freshwater fishes, we found numerous small ciliates in the gills and skin of crucian carp, Carassius carassius. Cursory examination indicated that the ciliate were very similar with Chilodonella sp. In this study, we described the morphometrics of this ciliate in detail and compared with other species of Chilodonella in the world. Numerous small ciliates were observed in the body surface, fins and gills of infected fish and excessive mucus production were seen in those fish. Sometimes ulcer was observed in the body of moribund fish. From the scrutinized observation of the parasite, it was identified as Chilodonella hexasticha. The parasite was dorsoventrally flattened body, without a notch in the posterior margin, and it measured 30-$45{\mu}m$ long and 15-$30{\mu}m$ wide. In number of kineties, the right band ciliature was 3-5 and the left band ciliature was 3-5. The right ventral ciliary band shaped arch and was longer than the left, straight band. It had a single oval macronucleus, 8-$15{\mu}m$ in diameter, a single micronucleus, 2-$4{\mu}m$ in diameter. The cytopharynx was reinforced by 10-16 conspicuous nematodesmata, which shaped like a tube and curved at its inner end. Two contractile vacuoles, one anteriorly at right and the second posteriorly at left were observed in wet mounts. This parasite reproduced by a simple division at $22{\pm}1^{\circ}C$.

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Effect of the Biological Activities of Ethanol Extract from Korean Traditional Kochujang Added with Sea Tangle (Laminaria longissima) (다시마 분말을 첨가한 전통고추장 에탄올 추출물의 생리활성 효과)

  • 함승시;최승필;오상화;이득식
    • Food Science and Preservation
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    • v.9 no.1
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    • pp.1-7
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    • 2002
  • This study was carried out to investigate antimutagenic and anticancer effects of Korean traditional Kochujang added with sea tangle (Laminuia longissima). Most of the mineral content in Kochujang added with sea tangle was increased when compared to traditional Kochujang. In the Ames test, the inhibition rate of ethanol extract (200 $\mu\textrm{g}$/plate) of Kochujang added with 5% sea tangle in the S. typimurium TA100 strain showed 87.2% against the mutagenesis induced by MNNG. And also, the inhibition rate of ethanol extract (200 $\mu\textrm{g}$/plate) of Kochujang added with 5% sea tangle in the S. typhimurium TA98 and TA100 strains was 62.9% and 71.6%, respectively, against the mutagenesis induced by 4NQO. The suppression under the same condition against B($\alpha$)P and Trp-P-1 in the TA98 and TA100 strains showed 70.2% and 80.8%, and 62.9% and 73.1%, respectively. In the anticancer effects, the treatment of 1.0 mg/mL Kochujang added with 5% sea tangle showed strong cytotoxicity of 78.6% and 79.4% against KATOⅢ and HepG2, respectively.

Antimutagenic and Anticancer Effects of Ethanol Extract from Korean Traditional Doenjang Added Sea Tangle (다시마 분말을 첨가한 전통된장 에탄을 추출물의 항돌연변이성 및 항암효과)

  • 최승필;이의용;이득식;함승시
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.31 no.2
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    • pp.322-328
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    • 2002
  • This study was carried out to investigate antimutagenic and anticancer effects of ethanolic extract of Korean traditional doenjang added sea tangle. Most of the mineral content of doeniang was increased by addition of sea tangle. In the Ames test, the antimutagenic effect of ethanol extract of Korean traditional doenjang added 5% sea tangle was higher than that of control (no additive), 10%, and 15% sea tangle additions. The inhibition rate of ethanol extract (200$\mu\textrm{g}$/plate) of doenjang added 5% sea tangle in the S. typhimurium TA100 strain showed 97.0% inhibition against the mutagenesis induced by MNNG. In addition, the suppression of ethanol extract (200$\mu\textrm{g}$/plate) of doenjang added 5% sea tangle in the S. typhimurium TA98 and TA100 strains showed 60.2% and 69.1% inhibition respectively, against the mutagenesis induced by 4NQO. The suppressions under the same condition against B($\alpha$ )P and Trp-P-1 in the TA98 and TA100 strains were 71.7% and 87.3%, and 66.6% and 80.8%, respectively. In the anticancer effects, the cytotoxicity of doenjang added 5% sea tangle on the cell lines with human lung carcinoma (A549), human hepatocellular carcinoma (HepG2), and human gastric carcinoma (KATOIII) were inhibited with increasing the extract concentration. The treatment of 1.0 mg/mL Doenjang added 5% sea tangle showed strong cytotoxicity of 56.4%, 87.67%, and 89.5% against A549, HepG2, and KATOIII, respectively.

Adaptive Response Induced by Low Dose Ionizing Raditation in Human Cervical Carcinoma Cells

  • Kim, Jeong -Hee;Lee, Kyung -Jong;Cho, Chul -Koo;Yoo, Seong -Yul;Kim, Tae -Hwan;Ji, Young -Hoon;Kim, Sung -Ho
    • Archives of Pharmacal Research
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    • v.18 no.6
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    • pp.410-414
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    • 1995
  • Adaptive response induced by low dese .gamma.-ray irradiation in human cervical carcinoma cells was examined. Cells were exposured to low dose of .gamma.-ray irradiation in human cervical carcinoma cells was examined. Cells were exposured to low dose of .gamma.-ray (1-cGy) followed by high doses of r-ray irradiation (0,1,2,3,5,7 and 9Gy for chlnogenic assay or 1.5Gy for micronucleus assay) with various time intervals. Survival fractions of cells in both low dose-irradiated and unirrated groups were analyzed by clonogenic assay. Surviva fractions of low dose-irradiated in cell survival was maximum when low and high dose irradiation time interval was 4 hr. Frequencies of micronuclei which is an indicative of chromosome aberration were also enutained from survival fractions analyzed by clonogenic assay, maximum when low and high dose irradiation time interval was 4hr. Frequencies of micronuclei which is an indicative of chromosome aberration were also enumerated in both low dose-irradiated and unirradiated groups. In consiststent with the result obtained from survival fractions analyzed by clonogenic assay, maximum reduction in frquencies of micronuclei was observed when low dose radiation was given 4 hr prior to high response to subsequent high dose .gamma.-ray irradiation in human cervical carcinomal cells. Our data suggest that one of the possible mechanisms of adaptive response induced by low dose rediation is the increase in repair of DNA double strand breaks in low dose radiation-adapted cells.

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Analysis of Micronuclei and Its Association with Genetic Polymorphisms in Hospital Workers Exposed to Ethylene Oxide (에틸렌옥사이드(Ethylene oxide)에 노출된 병원 근로자들의 소핵 빈도와 유전적 감수성 지표와의 연관성)

  • Lee, Sun-Yeong;Kim, Yang-Jee;Choi, Young-Joo;Lee, Joong-Won;Lee, Young-Hyun;Shin, Mi-Yeon;Kim, Won;Yoon, Chung-Sik;Kim, Sung-Kyoon;Chung, Hai-Won
    • Journal of Environmental Health Sciences
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    • v.37 no.6
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    • pp.429-439
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    • 2011
  • Objectives: Ethylene oxide (EtO) is classified as a human carcinogen, but EtO is still widely used to sterilize heat-sensitive materials in hospitals. Employees working around sterilizers are exposed to EtO after sterilization. The aim of the present study was to assess the exposure of EtO level, coupled with occupationally induced micronuclei from hospital workers. The influence of genetic polymorphisms of detoxifying genes (GSTT1 and GSTM1) and DNA repair genes (XRCC1 and XRCC3) on the frequencies of micronuclei in relation to exposure of EtO was also investigated. Methods: The study population was composed of 35 occupationally exposed workers to EtO, 18 student controls and 44 unexposed hospital controls in Korea. Exposure to EtO is measured by passive personal samplers. We analyzed the frequencies of micronuclei by performing cytokinesis-block micronucleus assay (CBMN assay) and GSTM1, GSTT1, XRCC1, and XRCC3 were also genotyped by performing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The frequencies of micronuclei in EtO exposure group, student controls and hospital controls were $18.00{\pm}7.73$, $10.47{\pm}7.96$ and $13.86{\pm}6.35$ respectively and their differences were statistically significant, but no significant differences according to the level of EtO were observed. There was a dose-response relationship between the frequencies of micronuclei and cumulative dose of EtO, but no significantly differences were observed. We also investigated the influence of genetic polymorphisms (GSTM1, GSTT1, XRCC1, and XRCC3) on the frequencies of micronuclei, but there were no differences in the frequencies of micronuclei by genetic polymorphisms. Conclusions: The frequencies of micronuclei in EtO exposure group was significantly higher than control groups. A dose-response relationship was found between the level of EtO exposure and the frequencies of micronuclei, but no statistically differences were observed. We also found that the frequencies of micronuclei were increased according to cumulative EtO level. There was no association of the genetic GSTM1, GSTT1, XRCC1, and XRCC3 state with the frequency of micronuclei induced by EtO exposure.

Frequency of Micronuclei in Lymphocytes Following Gamma and Fast-neutron Irradiations (방사선 조사량에 따른 인체 정상 림파구의 미세핵 발생빈도)

  • Kim Sung-Ho;Cho Chul-Koo;Kim Tae-Hwan;Chung In-Yong;Yoo Seong-Yul;Koh Kyoung-Hwan;Yun Hyong-Geun
    • Radiation Oncology Journal
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    • v.11 no.1
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    • pp.35-42
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    • 1993
  • The dose response of the number of micronuclei in cytokinesis-blocked (CB) lymphocytes after in vitro irradiation with $\gamma$-rays and neutrons in the 5 dose ranges was studied for a heterogeneous population of 4 donors. One thousand binucleated cells were systematically scored for micronuclei. Measurements performed after irradiation showed a dose-dependent increase in micronuclei (MN) frequency in each of the donors studied. The dose-response curves were analyzed by a linear-quadratic model, frequencies per 1000 CB cells were ($0.31{\pm}0.049$)D+($0.0022{\pm}0.0002)D^2+(13.19{\pm}1.854) (r^2=1.000,\;X^2=0.7074,\;p=0.95$) following $\gamma$ irradiation, and ($0.99{\pm}0.528$)\;D+(0.0093{\pm}0.0047)\;D^2+(13.31{\pm}7.309)\;(r^2=0.996,\;X^2=7.6834,\;p=0.11) following neutrons irradiation (D is irradiation dose in cGy). The relative biological effectiveness (RBE) of neutrons compared with $\gamma$-rays was estimated by best fitting linear-quadratic model. In the micronuclei frequency between 0.05 and 0.8 per cell, the RBE of neutrons was $2.37{\pm}0.17$. Since the MN assay is simple and rapid, it may be a good tool for evaluating the $\gamma$-ray and neutron response.

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