• Title/Summary/Keyword: Mutation-positive control

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Bacterial Reverse Mutation Test of CP pharmacopunture (세균을 이용한 CP 약침의 복귀돌연변이 시험)

  • Hwang, Ji Hye;Ku, Jaseung;Jung, Chul
    • The Journal of Korean Medicine
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    • v.41 no.3
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    • pp.55-65
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    • 2020
  • Objectives: This study aimed to evaluate the toxicity of CP pharmacopunture using bacterial reverse mutation test. Methods: To determine the mutagenic potential of CP pharmacopunture, histidine requiring Salmonella typhimurium (TA98, TA100, TA1535, and TA1537) and tryptophan requiring Escherichia coli (WP2uvrA, pKM101) strains were used. The negative (normal saline solution) and positive (Sodium azide, 2-Nitrofluorene, 2-Aminoanthracene, 9-Aminoacridine, and 4-Nitroquinoline N-oxide) control groups were used. To determine the dose levels of the main study, a dose range-finding study was conducted. Results: As a results of the dose range-finding study, the growth inhibition by CP pharmacopunture was not evident at any dose levels in the absence and presence of metabolic activation. As a results of the main study, the mean number of revertant colonies was less than twice when compared to the negative control values at all dose levels of the CP pharmacopuncture in the presence and absence of metabolic activation, showing no dose-related increase. In the positive control group, the number of revertant colonies was markedly increased by more than twice when compared to the negative control group. Conclusion: According to the results of this study, CP pharmacopunture did not show any signs of mutagenic potential.

Micronucleus Test in Bone Marrow Cells and Bacterial Reverse Mutation Assay of HMC05 (HMC05의 경구투여 소핵시험 및 복귀돌연변이 시험)

  • Shin, Heung-Mook
    • The Korea Journal of Herbology
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    • v.25 no.2
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    • pp.137-144
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    • 2010
  • Objectives : We investigated genetic toxicity of HMCO5 using the Micronucleus Test in bone marrow cells of mice and Bacterial Reverse Mutation Assay in plate incorporation method according to OECD Guidelines and KFDA Guidelines. Methods : 1. Micronucleus test: The male rats were divided into 5 groups, respectively; G(1), treated with distilled water: G(2), treated with 1250mg/kg HMC05: G(3), treated with 2500mg/kg HMC05, G(4), treated with 5,000mg/kg HMC05; G(5), treated with Cyclophosphamide $H_2O$. Sterilized distilled water and HMC05 were administered for two consecutive days. Cyclophosphamide $H_2O$ was administered once on the day of 2nd administration. 2. Bacterial Reverse Mutation Aassay: Experimental groups were divided into two groups: with S-9mix(+S) or without S-9mix(-S). Each group treated with sterilized distilled water only, HMCO5(62, 185, 556, 1,667, $5,000{\mu}g$/plate) and, positive vehicles(Sodium azide, 2-Aminoanthracene, 4-Nitroquinoline N-oxide, ICR 191), respectively. Results : HMC05 did not show any changes in the number of micronucleated polychromatic erythrocytes(MNPCE) among 200 polychromatic erythrocytes compare to negative control. However, there were significant (p<0.01) increase with CPA in MNPCE. In Bacterial Reverse Mutation Aassay, no significant increases in the number of revertant colonies compared to (삭제) negative control were detected in all concentrations of HMC05. Conclusions : These results indicate that HMC05 did not show any genotoxicity against in Micronucleus test and Bacterial Reverse Mutation Aassay.

Genotoxicity Evaluation Using Reversion Mutation Test of SU-Eohyeol Pharmacopuncture (SU어혈약침의 복귀돌연변이시험을 이용한 유전독성평가)

  • Ku, Jaseung;Hwang, Ji Hye
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.36 no.4
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    • pp.113-119
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    • 2022
  • SU-Eohyeol pharmacopuncture(SUEP) was developed by adding Cervi Pantotrichum Cornu to Jungsongouhyul pharmacopuncture. This genotoxicity evaluation was performed to evaluate the mutagenic potential of the test substance SUEP agent using histidine, which requires strains of Salmonella typhimurium (TA98, TA100, TA1535, TA1537), and tryptophan, which requires Escherichia coli (WP2uvrA) strain in the presence and absence of metabolic activation. According to the results of the dose range finding study conducted prior to the main study, the dose levels of the test substance in the main study were determined as 100, 50, 25, 12.5, 6.25%, and positive and negative controls were established. As a result of the main study, the mean number of revertant colonies compared to negative controls was less than 2-fold at all dose levels of SUEP in all strains with and without metabolic activation. In the positive control group, the mean number of revertant colonies for each strain was markedly increased by more than two times compared to the negative control group. Based on the result of this study, the test substance, SUEP did not show any indication of mutagenic potential under the conditions of this study.

Factors associated with effectiveness of and rash occurrence by Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in patients with non-small cell lung cancer (비소세포폐암 환자에 있어서 Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors의 약효 및 rash 발생과 관련한 인자에 대한 연구)

  • Bae, Na-Rae;Choi, Hye-Jin;Lee, Byung-Koo;Gwak, Hye-Sun
    • Korean Journal of Clinical Pharmacy
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    • v.18 no.2
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    • pp.75-83
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    • 2008
  • Purpose: Currently lung cancer ranks second in cancer for incidence rate and is a disease that ranks first for a death rate by cancerous growth because it is already advanced at the time of diagnosis. The purpose of this paper was to analyze the factors that affect the effectiveness of and rash occurrence by Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) in patients with non-small cell lung cancer. Methods: A retrospective chart review of 100 patients, who took EGFR TKI (erlotinib, gefitinib) among patients who were diagnosed with non-small cell lung cancer in a Hospital in Korea between May 2005 and February 2008, was conducted. The drug effectiveness was evaluated by Response Evaluation Criteria In Solid Tumor. Results: EGFR mutation was the only factor associated with drug response (complete response and partial response). When stable disease was added to drug response as the evaluation parameter, ECOG and rash as well as EGFR mutation were found to be important factors. Survival, however, was not affected by EGFR mutation. The factors influenced on survival were older age (${\geq}65$), low ECOG ($1{\sim}2$), adenocarcinoma and rash. In the case of rash, group with EGFR mutation or low ECOG showed significantly higher chance of occurrence. There was no significant difference in rash occurrence between gefitinib and erlotinib groups. Conclusions: Based on the results, EGFR mutation positive and low ECOG ($1{\sim}2$) were significantly important factors for both effectiveness of EGFR TKI and rash occurrence. Also, rash itself was found to be an independently significant factor for the disease control and survival. Therefore, while administering EGFR TKI, patients who have the factors associated with rash occurrence should be closely monitored for effective and safe drug therapy.

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Interferon Apha 2b for Treating Patients with JAK2V617F Positive Polycythemia Vera and Essential Thrombocytosis

  • Zhang, Zhi-Rong;Duan, Yan-Chao
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.4
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    • pp.1681-1684
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    • 2014
  • Objective: To investigate interferon (IFN) alpha 2 b for treating patients with JAK2V617F positive polycythemia vera (PV) and essential thrombocytosis (ET). Methods: Interferon alpha 2 b was used to treat patients with JAK2V617F positive PV and ET. In control group, hydroxyurea was used. Endpoint of study was to compare rates of hematological and molecular remission. Results: Patients in the interferon alpha 2 b group achieved higher rates of hematologic and molecular remission than patients in the hydroxyurea group, with a lower incidence of thrombosis. Conclusion: Compared with hydroxyurea, interferon alpha 2 b could reduce JAK2V617F load for patients with PV and ET, and achieve higher molecular remission, improve treatment efficacy and reduce complications.

Low-dose Epidermal Growth Factor Receptor (EGFR)-Tyrosine Kinase Inhibition of EGFR Mutation-positive Lung Cancer: Therapeutic Benefits and Associations Between Dosage, Efficacy and Body Surface Area

  • Hirano, Ryosuke;Uchino, Junji;Ueno, Miho;Fujita, Masaki;Watanabe, Kentaro
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.2
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    • pp.785-789
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    • 2016
  • A key drug for treatment of EGFR mutation-positive non-small cell lung cancer is epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). While the dosage of many general anti-tumor drugs is adjusted according to the patient body surface area, one uniform dose of most TKIs is recommended regardless of body size. In many cases, dose reduction or drug cessation is necessary due to adverse effects. Disease control, however, is frequently still effective, even after dose reduction. In this study, we retrospectively reviewed the characteristics of 26 patients at Fukuoka University Hospital between January 2004 and January 2015 in whom the EGFR-TKI dose was reduced with respect to progression free survival and overall survival. There were 10 and 16 patients in the gefitinib group and the erlotinib group, respectively. The median progression-free survival in the gefitinib group and the erlotinib group was 22.4 months and 14.1 months, respectively, and the median overall survival was 30.5 months and 32.4 months, respectively. After stratification of patients by body surface area, the overall median progression-free survival was significantly more prolonged in the low body surface area (<1.45 m2) group (25.6 months) compared to the high body surface area (>1.45 m2) group (9.7 months) (p=0.0131). These results indicate that low-dose EGFR-TKI may sufficiently control disease without side effects in lung cancer patients with a small body size.

Genotoxicity Study of GST Extract (GST 추출물의 유전독성평가)

  • Lee, Chul Wha;Han, Jong Min;Lee, Mi Young;Jung, In Chul;Jin, Mirim;Kim, Seung Hyung;Park, Yang Chun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.28 no.6
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    • pp.621-629
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    • 2014
  • This study aimed to evaluate the genotoxicity of GST (Gamisasangja-tang). For examining genotoxicity, we carried out bacterial reverse mutation assay, chromosome aberration assay, micronucleus induction test according to OECD guidelines. Bacterial reverse mutation assay: In GST treating group, regardless of existence S9 mix, revertant colonies counts appeared to be less than twice of negative control group and dose dependent increase. In positive control group, revertant colonies counts were shown to be more than twice of negative control croup. Chromosome aberration assay: All cell line showed repetition rate of abnormal chromosome aberration less than 5%, regardless of treating time, existence of S9 mix, and no significant change ($p{\succeq}0.05$) compared with negative control group. Micronucleus induction test: Micronucleated polychromatic erythrocytes (MNPCE) repetition rate of Polychromatic erythrocytes (PCE) showed no significant changes compared with negative control group ($p{\succeq}0.05$). PCE portion of total erythrocytes also showed no significant changes ($p{\succeq}0.05$). Our results showed that GST didn't induce any genotoxicity.

Mutagenicity Studies on Nonspecific Immunostimulator BARODON® (비특이 면역증강제 BARODON®에 대한 유전독성시험)

  • 서민수;조성대;안남식;정지원;양세란;박준석;박기수;홍인선;조은혜
    • Toxicological Research
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    • v.19 no.2
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    • pp.141-146
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    • 2003
  • A nonspecific immunostimulator $BARODON^{\circledR}$ was tested for mutagenicity using Ames Salmonella tester strains TA98, TA1 00, TA 102, TA 1535 and TA 1537 with or without metabolic activation (59 mix). None of the fresh species showed mutagenicity. In the reverse mutation test using Salmonella phimurium TA98, TA100, TA102, TA1535 and TA1537 did not increase the number of revertants at all doses tested (5, 2.5 or 1.25 mg/ml). Chromosome aberration test was carried out in Chinese hamster lung (CHL) cell line. The cells were treated with $BARODON^{\circledR}$ (1, 0.5 or 0.25 mg/ml), while positive control group was treated with Mitomycin C (0.1 mg/ml). The results show that there is no statistically significant difference between positive control and treatment groups. In mouse micronucleus test, there was significant increase in the ratio of micronucleated polychromatic erythrocyte (MNPCE) in the high dose group (10% $BARODON^{\circledR}$), while there is no significance between control and low (2.5% $BARODON^{\circledR}$) or middle (5% $BARODON^{\circledR}$ dose groups. Taken together, this results suggest that below 5% $BARODON^{\circledR}$ might not have mutagenic potential in vitro and vivo systems.

A Case-control Study for Assessment of Risk Factors of Breast Cancer by the p53 Mutation (p53 유전자 돌연변이에 따른 유방암의 위험 요인 구명을 위한 환자-대조군 연구)

  • Kim, Heon;Ahn, Se-Hyun;Lee, Moo-Song
    • Journal of Preventive Medicine and Public Health
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    • v.31 no.1 s.60
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    • pp.15-26
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    • 1998
  • p53 is the most frequently mutated gene in female breast cancer tissues and the prognosis of breast cancer could be changed by mutation of the gene. This study was performed to examine risk factors for breast cancer subtypes classified by p53 mutation and to investigate the roles of p53 gene mutation in carcinogenesis of breast cancer. The study subjects were 81 breast cancer patients and 121 controls who were matched to cases 1:1 or 1:2 age, residence, education level and menopausal status. All the subjects were interviewed by a well-trained nurse with standardized questionnaire on reproductive factors, and wire asked to fill the self-administrative food frequency questionnaire. p53 gene mutation in the cancer tissue was screened using polymerase chain reaction (PCR)-single strand conformational polymorphism (SSCP) method. Mutation type was identified by direct sequencing of the exon of which mobility shift was observed in SSCP analysis. Mutations were detected in p53 gene of 25 breast cancer tissues. By direct sequencing, base substitutions were found in 20 cancer tissues (10 transition and 10 transversion), and frame shift mutations in 5 (4 insertions and 1 deletion). For the whole cases and controls, risk of breast cancer incidence decreased when the parity increased, and increased when intake amount of total calory, fat, or protein increased. Eat and protein were statistically significant risk factors for breast cancer with p53 mutation. For breast cancer without p53 mutation, protein intake was the only significant dietary factor. These results suggest that causes of p53 positive breast lancer would be different from those of p53 negative cancer, and that dietary factors or related hormonal factors induce mutation of p53, which may be the first step of breast cancer development or a promoter following some unidentified genetic mutations.

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Effects of carbendazim on DNA, gene and chromosome (살균제 carbendazim이 DNA, 유전자 및 염색체에 미치는 영향)

  • Lee, Je-Bong;Sung, Pil-Nam;Jeong, Mi-Hye;Shin, Jin-Sup;Kang, Kyu-Young
    • The Korean Journal of Pesticide Science
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    • v.8 no.4
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    • pp.288-298
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    • 2004
  • Benzimidazole pesticide carbendazim that is effective against a wide range of fungal plant pathogens is a protective, eradicant, and systemic fungicide. For genetic toxicity evaluation of carbendazim on DNA, genes and chromosome, were investigated with chromosome aberration, bacterial reverse mutation, micronucleus test in mouse born marrow and DNA damage assay by single cell microgel electrophoresis. Substitution and frameshift mutation were not induce at variable concentration of carbendazim on Ames test with or without rat liver microsomal activation. For the result of chromosome aberration test, numerical changes of chromosome were detected at the concentrations higher than $4.0{\mu}g/m{\ell}$, but structural aberration was not induced. Positive control, Mitomycin-C and captafol made a structural aberration, but numerical change of chromosome did not appear. In the micronucleus test for mouse born marrow, carbendazim was negative, but was weak positive in DNA damage assay by single cell microgel electrophoresis because of increased DNA moving length of 20% to control.