• 제목/요약/키워드: Carcinogenicity

검색결과 202건 처리시간 0.027초

A close Relationship between Carcinogenicity and Self-atom Polarizability Index of Polycyclic Aromatic Hydrocarbons and Their Metabolites

  • Park, Byung-Kak;Suh, Man-Chul;Paek, U-Hyon
    • Bulletin of the Korean Chemical Society
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    • 제7권3호
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    • pp.183-185
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    • 1986
  • Self-atom polarizability were calculated for 17 polycyclic aromatic hydrocarbons and their metabolites by LCAO-MO method and examined the relation with the carcinogenicity. It has been found that ${\pi}_{1.2.4}$, the sum of self-atom polarizability of 1, 2 and 4 positions forming trans-butadiene frame in a compound, agree quite well with the observed carcinogenic activity, and also, ${\pi}_{1.2.4}$ value increase with the metabolic activiting in agreement with the experimental facts that parent carcinogens activated with metabolism. Accordingly, we suggest that the 1, 2 and 4 positions in the carcinogenic compounds play the most important role in the process of chemical carcinogenesis, and also self-atom polarizability, as one of theoretical reactivity indices, is to be used as a measure of carcinogenic activity.

Establishment of a Stable Cell Line Expressing Green Fluorescence Protein-fused Hypoxia Inducible Factor-1α for Assessment of Carcinogenicity of Chemical Toxicants

  • Kim, Sung-Hye;Seo, Hee-Won;Lee, Min-Ho;Chung, Jin-Ho;Lee, Byung-Hoon;Lee, Mi-Ock
    • Toxicological Research
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    • 제25권4호
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    • pp.189-193
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    • 2009
  • Hypoxia inducible factor $1\alpha$ (HIF-$1\alpha$) is a potential marker of carcicnogenesis since it is overexpresssed in many human cancers such as brain, breast, and uterus, and its role has implicated in tumor cell growth and metastasis. In this study, we established a stable cell line that express green fluorescence protein (GFP)-fused hypoxia inducible factor $1\alpha$ (HIF-$1\alpha$) and evaluated the potential use of this cell line for assessment of carcinogenicity of chemical toxicants. Western blot analysis as well as fluorescence measurements showed that protein-level of GFP-HIF-$1\alpha$ was significantly enhanced in a dose-dependent manner upon treatment of hypoxia mimicking agents such as dexferrioxamine and $CoCl_2$. Well-Known tumor promoters such as mitomycin and methyl methanesulfonate. significantly induced the fluorescence intensity of GFP-HIF-$1\alpha$, whereas the known negative controls such as o-anthranilic acid and benzethonium chloride, did not. These results indicate that HIF-$1\alpha$ could be a biological parameter for detection of tumor initiators/promoters and suggest that the GFP-HIF-$1\alpha$ cell line is a useful system for screening of carcinogenic toxicants.

Biphenyl 취급사업장의 작업환경 및 유해성 평가 (Working Environment and Risk Assessment of Biphenyl in Workplace)

  • 김현영
    • 한국가스학회지
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    • 제18권2호
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    • pp.55-61
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    • 2014
  • 본 연구는 고무 화학제품의 제조에 연화제로 많이 사용되며 국제암연구소(IARC)에 발암추정물질(2A)로 등록되어 있는 Biphenyl에 대해 국내 취급사업장에 대한 작업환경 측정과 근로자 노출량 산출, 그리고 유해성에 따른 위험성을 결정하였다. 노출시나리오를 바탕으로 노출량 산출 결과는 각각 $1.0{\times}10^{-2}$, $4.2{\times}10^{-4}$, $7.0{\times}10^{-6}mg/m^3$이었으며, 위해성 분류에 따라 산출한 $RfC_{work}$는 발암성 0.21, 표적독성(경구) 2.13, 표적독성(흡입) 0.53, 발달독성 $0.31mg/m^3$으로 산출되었다. 유해성 및 노출평가의 결과를 바탕으로 한 위험성은 발암성 0.57, 비발암성(발달독성) 0.39로 도출되어, 1이하의 비교적 낮은 위험도로 나타났으나, Biphenyl은 일부 유해성이 확인되었으며 사용량이 많고 취급 부주의시 근로자에 직접 노출될 수 있어 취급근로자의 건강장해 예방을 위해 노출 감시가 필요한 물질로 판단되었다.

2년 장기 발암성 검색법의 이슈 (Issues in 2-year Long-term in vivo Carcinogenicity Assay)

  • 손우찬;김배환;장동덕;한범석;김종춘;이제봉;신진섭;김형진
    • 농약과학회지
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    • 제8권4호
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    • pp.239-254
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    • 2004
  • 2년 발암성 독성시험의 실시와 평가에 대해서는 많은 논란이 있었다. 2년 발암성 시험의 유용성에 대한 많은 비판에도 불구하고 설치류를 이용한 발암성 시험은 사람의 발암성을 예측 할 수 있는 유일한 평가 시스템으로 인식되어 있으며, 아직 이를 대체할 만한 평가 방법은 없다고 할 수도 있다. 그간 규제기관과 학계에서는 다양한 발암성 평가모델을 제시해 왔지만 이런 시험 모델들이 과학적 타당성과 검증된 데이터에 근거하는지에 대해서는 논란이 있다. 2년 설치류 발암성 시험에 제기되는 문제들 즉, 종 및 품종의 선택, 용량설정, 시험기간, 군당 동물의 수, 배경병변, 검사항목, 시험 종료시 측정항목, 병리의 피어리뷰, 통계, 대체시험 모델, 종양의 평가, 그리고 위해성 평가 등에 대하여 검토하였다.

저산소유도인자 HIF-1, 암 억제인자 P53과 고아 핵수용체 Nur77의 발현을 지표로 하는 발암독성예측 세포주의 개발 (Establishment of Reporter Cell Lines that Monitor Activities of Hypoxia Inducible Factor-1, P53 and Nur77 for Assessment of Carcinogenicity)

  • 홍일;서희원;이민호;김지원;정진호;이병훈;이미옥
    • Toxicological Research
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    • 제23권3호
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    • pp.231-238
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    • 2007
  • Evaluation of potentials of chemicals to alter expression of genes that are involved in carcinogenesis may serve useful tools in toxicological research. In this investigation, we developed reporter cell lines that expressed luciferase in response to transactivation of hypoxia inducible factor-1, P53 tumor suppressor and Nur77 of which roles have been well established in cancer development and progression. Whereas these reporter cell lines displayed low constitutive backgrounds, the reporter activities were significantly enhanced in response to $desferriosamine/CoCl_2$, adriamycin or 6-mercaptopurine, which are hypoxia mimicking chemicals, P53 activator or Nur77 inducer, respectively. The activation of the reporter was time- and dose-dependent. Known tumor initiators and promoters, such as phorbol 12-myristate 13-acetate and phorbol 12, 13-dicaprinate induced the reporter activity at as low as 10nM in these stable cell lines. Further, known anti-tumor promoters, such as ascorbic acid and ${\beta}-carotene$ repressed the reporter activities. These results indicate that our stable reporter cell lines could serve as a useful system for rapid assessment of carcinogenicity of toxic chemicals.

Gasoline 취급 사업장의 작업환경 측정 및 위해성 평가 (Working Environment and Risk Assessment of Gasoline in Workplace)

  • 김현영
    • 한국가스학회지
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    • 제18권4호
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    • pp.1-7
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    • 2014
  • 화학물질로부터 근로자의 건강보호를 위해 사용량이 많으나 작업환경 및 유해성 평가 자료가 부족한 gasoline에 대해 유해성(hazards)을 조사하고 국내 취급실태 및 일부 취급 사업장의 작업환경 측정을 통해 위해성(risk assessment)을 평가하였다. 연구결과 gasoline은 생식독성 추정 및 생식세포 변이원성 물질인 1B, 그리고 IARC Group 2B, ACGIH A3 물질이었다. 작업환경 측정결과는 TLV-TWA 기준 $900mg/m^3$미만이었으며, 유해성 평가결과 발암 $RfC_{(Worker)}$$0.3mg/m^3$, 만성흡입독성 $RfC_{(Worker)}$$2.7mg/m^3$, 발달독성 $RfC_{(Worker)}$$2.7mg/m^3$이었다. 그리고 위험도 평가에서 발암성은 459, 만성흡입독성은 51, 발달독성은 51이었으며, 이를 토대로 한 gasoline의 위험도는 1을 초과하는 물질로 평가되었다.

작업장 화학물질 독성예측을 위한 독성발현경로의 응용과 전망 (Adverse Outcome Pathways for Prediction of Chemical Toxicity at Work: Their Applications and Prospects)

  • 임경택;최흥구;이인섭
    • 한국산업보건학회지
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    • 제29권2호
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    • pp.141-158
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    • 2019
  • Objectives: An adverse outcome pathway is a biological pathway that disturbs homeostasis and causes toxicity. It is a conceptual framework for organizing existing biological knowledge and consists of the molecular initiating event, key event, and adverse output. The AOP concept provides intuitive risk identification that can be helpful in evaluating the carcinogenicity of chemicals and in the prevention of cancer through the assessment of chemical carcinogenicity predictions. Methods: We reviewed various papers and books related to the application of AOPs for the prevention of occupational cancer. We mainly used the internet to search for the necessary research data and information, such as via Google scholar(http://scholar.google.com), ScienceDirect(www.sciencedirect.com), Scopus(www.scopus. com), NDSL(http: //www.ndsl.kr/index.do) and PubMed(http://www.ncbi.nlm.nih.gov/pubmed). The key terms searched were "adverse outcome pathway," "toxicology," "risk assessment," "human exposure," "worker," "nanoparticle," "applications," and "occupational safety and health," among others. Results: Since it focused on the current state of AOP for the prediction of toxicity from chemical exposure at work and prospects for industrial health in the context of the AOP concept, respiratory and nanomaterial hazard assessments. AOP provides an intuitive understanding of the toxicity of chemicals as a conceptual means, and it works toward accurately predicting chemical toxicity. The AOP technique has emerged as a future-oriented alternative to the existing paradigm of chemical hazard and risk assessment. AOP can be applied to the assessment of chemical carcinogenicity along with efforts to understand the effects of chronic toxic chemicals in workplaces. Based on these predictive tools, it could be possible to bring about a breakthrough in the prevention of occupational and environmental cancer. Conclusions: The AOP tool has emerged as a future-oriented alternative to the existing paradigm of chemical hazard and risk assessment and has been widely used in the field of chemical risk assessment and the evaluation of carcinogenicity at work. It will be a useful tool for prediction, and it is possible that it can help bring about a breakthrough in the prevention of occupational and environmental cancer.