• 제목/요약/키워드: genetic toxicology

검색결과 252건 처리시간 0.027초

Evaluation of the genetic toxicity of synthetic chemicals (V) -in vitro Chromosomal Aberration Assay with 17 chemicals in Chinese Hamster Lung Cells-

  • Ryu, Jae-Chun;Kim, Kyung-Ran;Kim, Youn-Jung;Choi, Hae-Yeon
    • 한국환경성돌연변이발암원학회지
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    • 제22권4호
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    • pp.215-222
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    • 2002
  • The detection of many synthetic chemicals used in industry that may pose a genetic hazard in our environment is of great concern at present. Since these substances are not limited to the original products, and enter the environment, they have become widespread environmental pollutants, thus leading to a variety of chemicals that possibly threaten the public health. In this respect, to regulate and to evaluate the chemical hazard will be important to environment and human health. The clastogenicity of 17 synthetic chemicals was evaluated in Chinese hamster lung fibroblast cells in vitro. Two most cytotoxic chemicals, dodecyl methacrylate (CAS No. 142-90-5) and 2-ethylhexyl methacrylate (CAS No. 688-84-6), among 17 chemicals tested revealed no clastogenicity in the range of 0.0165-0.066 $\mu\textrm{g}$/$m\ell$ and 0.006-0.024 $\mu\textrm{g}$/$m\ell$ both in the presence and absence of metabolic activation system, respectively. All 17 chemicals revealed no significant induction of chromosomal aberration both in the presence and absence of metabolic activation system in this assay. From the results of chromosomal aberration assay with 17 synthetic chemicals in Chinese hamster lung cells in vitro, we did not observed positive clastogenic results in this study.

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Genetic Variants at 6p21.1 and 7p15.3 Identified by GWASs of Multiple Cancers and Ovarian Cancer Risk: a Case-control Study in Han Chinese Women

  • Li, Da-Ke;Han, Jing;Liu, Ji-Bin;Jin, Guang-Fu;Qu, Jun-Wei;Zhu, Meng;Wang, Yan-Ru;Jiang, Jie;Ma, Hong-Xia
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권1호
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    • pp.123-127
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    • 2014
  • A recent study summarized several published genome-wide association studies (GWASs) of cancer and reported two pleiotropic loci at 6p21.1 and 7p15.3 contributing to multiple cancers including lung cancer, noncardia gastric cancer (NCGC), and esophageal squamous-cell carcinoma (ESCC) in Han Chinese. However, it is not known whether such genetic variants have similar effects on the risk of gynecologic cancers, such as ovarian cancer. Hence, we explored associations between genetic variants in 6p21.1 and 7p15.3 and ovarian cancer risk in Han Chinese women. We performed an independent case-control study by genotyping the two loci (rs2494938 A > G at 6p21.1 and rs2285947 A > G at 7p15.3) in a total of 377 ovarian cancer cases and 1,034 cancer-free controls using TaqMan allelic discrimination assay. We found that rs2285947 at 7p15.3 was significantly associated with risk of ovarian cancer with per allele odds ratio (OR) of 1.33 [95% confidence interval (CI): 1.08-1.64, P=0.008]. However, no significant association was observed between rs2494938 and ovarian cancer risk. Our results showed that rs2285947 at 7p15.3 may also contribute to the development of ovarian cancer in Han Chinese women, further suggesting pleiotropy of 7p15.3 in multiple cancers.

Muscle-Specific Creatine Kinase Gene Polymorphisms in Korean Elite Athletes

  • Kang, Byung-Yong;Kang, Chin-Yang;Lee, Kang-Oh
    • Toxicological Research
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    • 제19권2호
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    • pp.115-121
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    • 2003
  • In view of the importance of muscle-specific creatine kinase (CKMM) gene as a genetic factor for athletic performance, we investigate the relationship between elite athletic performance and two restriction fragment length polymorphisms (Ncol and Taql RFLPs) in the CKMM gene. Genomic DNA was extracted from white blood cells of 98 unrelated male Korean elite athletes and 04 sedentary controls, respectively. Two genetic polymorphisms in the CKMM gene were detected by the polymerase chain reaction and the digestion with restriction endonucleases, Ncol and Taql, respectively. There were no significant associations between two genetic polymorphisms in the CKMM gene and elite athletic performance or clinical parameters in our subjects. Therefore, these findings suggest that two genetic polymorphisms in the CKMM gene may not be useful as genetic markers to predict the athletic performance in male Koreans.

Gene Expression Profiling of Early Renal Toxicity Induced by Gentamicin in Mice

  • Oh, Jung-Hwa;Park, Han-Jin;Lim, Jung-Sun;Jeong, Sun-Young;Hwang, Ji-Yoon;Kim, Yong-Bum;Yoon, Seok-Joo
    • Molecular & Cellular Toxicology
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    • 제2권3호
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    • pp.185-192
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    • 2006
  • To elucidate the molecular mechanisms associated with early renal injury induced by gentamicin, the most commonly used antibiotics worldwide in the treatment of Gram-negative bacterial infections. We have identified genes differentially expressed at different duration of gentamicin administration. C57BL/6 female mice were treated daily with gentamicin (20 mg/kg, 100 mg/kg, and 200mg/kg) for 7 days and then sacrificed at day 1, 3, and 7 after administration. Standard blood biochemistry and histopathological observation indicative of nephrotoxicity were made. Total RNA was extracted from the kidney for microarray analysis using Affymetrix $GeneChip^{\circledR}$. Five hundred and seventy eight genes were identified as being either up-or down-regulated over 2-fold changes during early renal injury (p<0.05) and were analyzed by hierarchical clustering. The results showed that the genes involved in early immune responses were differentially regulated during early renal injury. Principal component analysis (PCA) confirmed sample separation according to the degree of renal toxicity. In addition, we identified two potential biomarkers that may predict early renal toxicity. This data may contribute to elucidate of the genetic events during early renal injury and to discover the potential biomarkers for nephrotoxicity induced by gentamicin.

Toxicological Evaluation of Oriental Herbal Medicine Kamijadowhan Preparations

  • Park, Young-Jin;Ryu, Jae-Chun;Choi, Seung-Hun;Kwon, Oh-Seung
    • 대한약학회:학술대회논문집
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    • 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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    • pp.289.2-290
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    • 2002
  • Choi group reported that Kamijadowhan (KMD). an oriental herbal medicine, has anti-angiogenic effects and it may be a potential agent for clinical chemoprevention since it inhibits angiogenesis. Objectives of this experiment are to investigate acute, genetic and reproductive/developmental toxicities of KMD preparations. Acute toxicity was performed after single administration of KMO (200-500 mg/kg) to mice. Supravital staining micronucleus assay was conducted using peripheral reticulocytes in mice. (omitted)

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Evaluation of the Genetic Toxicity of Synthetic Chemicals (IV) - Chromosomal Aberration Assay With 11 compounds in Chinese Hamster Lung Cells in vitro -

  • Kim, Kyung-Ran;Kim, Hyun-Joo;Kim, Min-Hee;Youn, Ji-Youn;Kwon, Oh-Seung;Ryu, Jea-Chun
    • 한국환경독성학회:학술대회논문집
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    • 한국환경독성학회 1996년도 제19회정기학술대회(The 19th Symposium of the Korean Society of Environmental Toxicology)
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    • pp.63-63
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    • 1996
  • We performed chromosomal aberration assay in Chinese Hamster Lung (CHL) cells in vitro to evaluate theclastogenicity of 11 synthetic chemicals which were listed in Toxicity Evaluation Program of Ministry of Environment of Republic of Korea in 1996. All of the chemicals were carried out MTT assay to determine the 50% cell growth inhibition concentration. All compounds were tested with and without metabolic activation system. Benzoyl chloride revealed positive result at $43\;\mu\textrm{g}/m{\ell}$ in the presence of metabolic activation system, and at 30.8, 61.5 and $123\;\mu\textrm{g}/m{\ell}$ in the absence of metabolic activation system. And p-phenoxy ethanol was observed as positive with the metabolic activation system, but negative without metabolic activation system. Especially 2-propyn-l-ol showed high frequency of pulverization and showed critical difference of cytotoxicity between with and without S9 mixture. Pulverizatiuon is not included in the frequency of structural aberration in our criteria. Dicyclopentadiene, methacrylic acid, aa-dimethylbenzyl hydroperoxide, benzylbutyl phthalate, and p-chlorophenal were revealed negative results.esults.

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The Sca I RFLP of Atrial Natriuretic Peptide Gene in Koreans

  • Kang, Byung-Yong;Bae, Joon-Seol;Kim, Ki-Tae;Lee, Kang-Oh
    • 한국환경독성학회:학술대회논문집
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    • 한국환경독성학회 2002년도 추계국제학술대회
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    • pp.165-165
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    • 2002
  • Hypertension is considered to be caused by a complicated combination of genetic and environmental factors. Atrial natriuretic peptide (ANP) has been to suppress renin activity and inhibit the synthesis and release of aldosterone. Therefore, Abnormalities of this peptide caused by genetic variation may be influence the blood pressure. The aim of present study was to examine the relationship between hypertension and Sca I RFLP of ANP gene in Korean population. The genotype distribution of this RFLP was significantly different between normotensives and hypertensives (P<0.05). However, this genetic marker was not significantly associated with any anthropometric parameters or plasma lipid concentrations in our study group. Therefore, our result suggest that Sca I RFLP of ANP gene may be useful as genetic marker in the ethiology of hypertension in Korean population, independent of any cardiovascular risk. factors studied.

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Ethnic Differences in the Metabolism of Toluene: Comparisons between Korean and Foreign Workers Exposed to Toluene

  • Kim, Ki-Woong;Won, Young Lim;Ko, Kyung Sun
    • Toxicological Research
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    • 제31권1호
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    • pp.25-32
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    • 2015
  • The objectives of this study were to investigate the individual characteristics, lifestyle habits, exposure levels, and genetic diversity of xenobiotic-metabolizing enzymes involved in toluene metabolism in Korean and foreign workers exposed to toluene at a manufacturing plant. This study was conducted to determine the effects of culture or ethnicity on toluene metabolism. The results showed that blood and urinary toluene concentrations were dependent on the level of exposure to toluene. We analyzed the correlation between toluene metabolism and genetic diversity in glutathione S-transferase (GST) (M1), GSTT1, and cytochrome p-450 (CYP) $2E1^*5$ as well as lifestyle habits (smoking, drinking, and exercise habits). The results revealed significant correlations between toluene metabolism and GSTM1 and GSTT1 genetic diversity, as well as smoking and exercise.

USE OF A MIXED METABOLIC ACTIVATION SYSTEM IN THE SALMONELLA REVERSE MUTATION TEST OF CHEMICAL CARCINOGENS

  • Oh, Goo-Taeg;Kim, Won-Yong;Park, Jae-Youn;Lee, Chang-Eop;Kim, Hwan-Mood
    • Toxicological Research
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    • 제4권2호
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    • pp.131-142
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    • 1988
  • The post-mitochondrial liver fractions (S-9) were prepared from rats and hamsters which have been treated with Aroclor 1254 (PCB) and the capacities of these S-9 fractions to generate mutagenic metabolites from several well known procarcinogens have been compared. Benzo(a)pyrene (B(a)P), 3-methylcholanthrene (3-MC), Aflatoxin B1(AFB1), 2-acetylamino-fluorene(AAF), and 2-aminofluorene (AF) were employed as promutagens in the Salmonella reverse mutation tests. Results showed that the rat and hamster S-9 fractions had differential abilities to produce mutagenic metabolites from a given promutagen.

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The Multi-Faceted Consequences of NRF2 Activation throughout Carcinogenesis

  • Christopher J. Occhiuto;Jessica A. Moerland;Ana S. Leal;Kathleen A. Gallo;Karen T. Liby
    • Molecules and Cells
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    • 제46권3호
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    • pp.176-186
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    • 2023
  • The oxidative balance of a cell is maintained by the Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway. This cytoprotective pathway detoxifies reactive oxygen species and xenobiotics. The role of the KEAP1/NRF2 pathway as pro-tumorigenic or anti-tumorigenic throughout stages of carcinogenesis (including initiation, promotion, progression, and metastasis) is complex. This mini review focuses on key studies describing how the KEAP1/NRF2 pathway affects cancer at different phases. The data compiled suggest that the roles of KEAP1/NRF2 in cancer are highly dependent on context; specifically, the model used (carcinogen-induced vs genetic), the tumor type, and the stage of cancer. Moreover, emerging data suggests that KEAP1/NRF2 is also important for regulating the tumor microenvironment and how its effects are amplified either by epigenetics or in response to co-occurring mutations. Further elucidation of the complexity of this pathway is needed in order to develop novel pharmacological tools and drugs to improve patient outcomes.