• Title/Summary/Keyword: Immunotoxicology

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Looking Inside the Cell for Mechanisms of Immunotoxicity: Experimental Design and Approaches Aimed Toward Elucidation of 2,3,7,8-Tetrachlor- dibenzo-p-dioxin-mediated B Cell Dysfunction

  • Norbert E. Kaminski;Kang, Jong-Soon
    • Toxicological Research
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    • v.17
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    • pp.205-210
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    • 2001
  • One of the major focuses and perhaps the greatest challenges during the past decade in the discipline of immunotoxicology has been the elucidation of the molecular mechanisms responsible for immunotoxicity by specific agents. Much is currently understood about the basic underlying intracellular processes that control leukocyte effector function. This fundamental information in cell biology can now be applied toward developing systematic approaches, through the application of cell and molecular biology techniques, to identify the intracellular targets and processes disrupted by immunotoxicants. The objective of this paper is two fold. First to discuss fundamental principles of experimental design aimed at elucidation of cellular mechanisms in immunotoxicology; and second to discuss the application of molecular biology techniques in characterizing the mechanism of TCDD-induced B cell dysfunction as a working example.

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Evaluation of Phototoxicity for Cosmetics and Alternative Method (화장품 광독성 평가와 동물대체시험법)

  • Lee, Jong-Kwon;Sin, Ji-Soon;Kim, Jin-Ho;Eom, Jun-Ho;Kim, Hyung-Soo;Park, Kui-Lea
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.31 no.3 s.52
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    • pp.245-251
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    • 2005
  • Safety is one of the key issue in the regulation of cosmetics. Cosmetic Act deals with it in Korea. The guidance for the testing cosmetic ingredients and their safety evaluation are prepared by Korea Food and Drug Administration. Ultraviolet radiation could Induce skin damage, edema, erythema, photoaging, immune dysfunction and skin cancer. Ultraviolet radiation is classified as Group 2A(probably carcinogenic to humans) by International Agenry for Reaserch on Cancer(IARC). The in vitro methodologies for evaluating the toxic potential of ingredients reported in the literature have not yet been sufficiently validated for use in areas other than the study for mutagenicity/genotoxicity, for pre-screening for severe irritancy, for screening of phototoxicity and for evaluating the percutaneous absorption. The 3T3 neutral red uptake photoxicity test (3T3 NRU PT) was accepted as OECD toxicity guideline in 2002. The 3T3 NRU PT is an in vitro method based on a comparison of the cytotoxicitv of a chemical when tested in the presence and in the absence of exposure to a non-cytotoxic dose of UVA/visible light.

Immunotoxicology Evaluation of New Drugs

  • Ahn, Chang-Ho;Kenneth L. Hastings
    • Toxicological Research
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    • v.17
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    • pp.211-216
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    • 2001
  • Drugs can have various adverse effects on the immune system including unintended immun-osuppression, induction of both drug-specific immune responses (including drug allergies) and non-specific immunostimulation (including autoimmune reactions), and direct activation of effector mechanisms (such as histamine release). As a practical matter, the Center for Drug Evaluation (CDER) relies on standard non-clinical toxicology studies to detect unintended immunosuppression. Specific assays using guinea pigs and mice are available to identify drugs that can induce immune-mediated dermal hypersensitivity reactions. Respiratory and systemic hypersensitivity and autoimmune reactions are more difficult to model in non-clinical studies. Unintended nonspecific immunstimulation can be detected in animal studies. CDER is currently developing specific guidance for evaluating potential drug immunotoxicity.

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Allergenicity Test of Genetically Modified Soybean in Sprague Dawley Rats

  • Chang, Hyun-Sung;Bae, Youn-Kyoung;Lim, Si-Kyu;Jeong, Tae-Cheon;Kim, Hyung-Soo;Chung, Seung-Tae;Kim, Dong-Sup;Nam, Doo-Hyun
    • Archives of Pharmacal Research
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    • v.24 no.3
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    • pp.256-261
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    • 2001
  • Allergenicity of genetically-modified (GM) soybean was evaluated in male Sprague Dawley rats. To confirm the GM soybean used in this study, the polymerase chain reaction (PCR) was performed using the chromosomal DNA of soybeans. The PCR result provided the clear discrimination of genetically-modified (GM) soybeans. To evaluate the allergenicity of GM soybean and non-GM control one, the soybean homogenate was sensitized subcutaneously 3 times a week for 3 weeks. The doses of soybean were 0, 2 and 20 mg/kg in the protein basis. A week after the last sensitization, antisera were recovered from individual animals. When the sera were injected intradermally on the clipped back of unsensitized rats with various dilutions, followed by a challenge with 20 mg/kg of soybean homogenate containing 1% Evans blue, no sign of passive cutaneous anaphylaxis reaction was detected. In addition, when the sera were treated in the cultures of peritoneal mast cells, the increase of histamine release by anti-(GM soybean) sera was not observed when compared to that by anti-(non-GM soybean) sera. The present results indicate that the GM soybean might not act as a strong allergen in male Sprague Dawley rats.

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Regulation of macrophage inflammatory protein-2 gene expression in response to 2,4-dinitrofluorobenzene in RAW 264.7 cells

  • Kim, Dong-Bum;Kim, Jin-Ho;Kwon, Sang-Hoon;Kim, Young-Jin;Lee, Soo-Hyoung;Lee, Young-Hee;Seo, Jae-Nam;Park, Cheung-Seog;Park, Kui-Lea;Kwon, Hyung-Joo
    • BMB Reports
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    • v.41 no.4
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    • pp.316-321
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    • 2008
  • Several skin sensitizers, like 2,4-dinitrofluorobenzene (DNFB), are known to provoke contact hypersensitivity responses after topical application. Here, we show that DNFB can upregulate macrophage inflammatory protein-2 (MIP-2) expression in RAW 264.7 cells via a mechanism that is largely dependent on mitogen-activated protein kinase (MAPK) signaling pathways. ELISA-based transcription factor activation assays and chromatin immunoprecipitation assays revealed that functional interaction between AP-1 and MIP-2 promoter element is necessary for MIP-2 gene expression by DNFB. Interestingly, topical application of DNFB to NC/Nga mice increased MIP-2 expression in dermis, suggesting that MIP-2 contributes to the leukocyte infiltration associated with atopic dermatitis. These results provide additional insight of the mechanism of contact hypersensitivity induced by contact sensitizers.

L-ASCORBIC ACID AND ARSENIC TRIOXIDE EXERT THE SYNERGISTIC EFFECT TO INDUCE THE GROWTH ARREST AND THE APOPTOSIS OF HUMAN ACUTE PROMYELOCYTIC LEUKEMIA, HL-60 VIA MODULATING REDOX STATUS, MAPK PATHWAY AND APOPTOSIS-RELATED FACTORS

  • Seong-Su Han;Sook J. Lee;Seung-Tae Chung;Juno H. Eom;Young-Joon Surh;Hye K. Park;Mary H. Park;Won S. Kim;Kihyun Kim
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10a
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    • pp.145-146
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    • 2001
  • There are increasing evidences that L-ascorbic acid (LAA) is selectively toxic to some types of tumors at physiological concentrations as a prooxidant, rather than antioxidant. However, the mechanism by which LAA initiates cellular signaling toward cell death is still unclear. Therefore, to determine whether LAA might be useful for the treatment of human acute promyelocytic leukemia (APL), HL-60 cells, the effects of LAA on proliferation, redox system, MAPK and induction of apoptotic cascades were investigated.(omitted)

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L-ASCORBIC ACID AND ARSENIC TRIOXIDE SYNERGISTICALLY REPRESS CONSTITUTIVE ACTIVATION OF NF- $\textsc{k}$B AND COX-2 EXPRESSION IN HUMAN ACUTE PROMYELOCYTIC LEUKEMIA, HL-60

  • Han, Seong-Su;Lee, Sook-J.;Chung, Seung-Tae;Eom, Juno-H.;Surh, Young-Joon;Park, Hye-K.;Park, Mary-H.;Kim, Won-S.;Kim, Ki-Hyun;Park, Keun-Chil;Kim, Jhin-Gook;Yang, Jung-Hyun;Yoon, Sung-S;Neil H.Riordan;HughD.Riordan;BruceF.Kimler;Park, Chan-H.
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10a
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    • pp.143-144
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    • 2001
  • Eukaryotic nuclear transcription factor, NF-B and cyclooxygenase-2 (COX-2) has been implicated in pathogenesis of many human diseases including tumor and are known to be activated by various external stimuli. Recently, increasing evidences have supported that L-ascorbic acid (LAA) is selectively toxic to some types of tumors at pharmacological concentrations as a prooxidant, rather than antioxidant.(omitted)

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Immunotoxicological Aspects of Pesticides (식품의 안전성면역에서 본 농약의 면역독성에 관하여)

  • 문창규
    • Journal of Food Hygiene and Safety
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    • v.1 no.1
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    • pp.97-106
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    • 1986
  • Pesticides constitute a unique group of biologically active chemicals in that they are produced for deliberate release into the environment, usually to produce some specific biocidal effect. Workers at all stages of pesticide production and application become exposed, at least on an occasional basis, while some experience routine exposure. The general population is, in turn, exposed to the residues, in air, water and food. This review is intended to survey the present knowledge of the immunotoxicity of 20 pesticides. As will be readily seen, knowledge of pesticide immunotoxicology to date is largely descriptive with only modest beginnings toward understanding mechanisms underlying the effects. In most cases the effects have not yet to be defined in immunological state, and just as little is presently known about how these chemicals exert their effects. There is an equally great gap in perceiving any relationship between the structure of a chemical and immunotoxicological potential.

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