• Title/Summary/Keyword: carcinogenicity study

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EFFECTS OF HYDROQUINONE ON NEOPLASTIC TRANSFORMATION OF HUMAN EPITHELIAL CELLS IN CULTURE (Hydroquinone이 인체 상피세포의 발암화에 미치는 영향)

  • Sohn, Jung-Hee;Kim, Chin-Soo
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.32 no.3
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    • pp.218-228
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    • 2010
  • Components of dental resin-based restorative materials are reported to leach from the filling materials even after polymerization. Hydroquinone (HQ) is one of the major monomers used in the dental resin and is known as a carcinogen. Thus, carcinogenic risk of HQ leaching from the dental resin becomes a public health concern. The present study attempted to examine the carcinogenic potentials of HQ on the human epithelial cell, which is the target cell origin of the most of oral cancers. Cytotoxicity of HQ was observed above 50${\mu}M$ as measured by LDH assay, indicating a relatively low toxicity of this substance in human epithelial cells. The parameters of neoplastic cellular transformation such as cell saturation density, soft agar colony formation and cell aggregation were analyzed to examine the carcinogenic potential of HQ. The study showed that 2-week exposure of HQ showed the tendency of increase in the saturation density and the significant enhancement of soft agar colony formation at the highest dose, 50 ${\mu}M$ only. It is suggested that HQ has a weak potential of carcinogenicity. When cells were treated with HQ and TPA, a well-known tumor promoter, the parameters of neoplastic cellular transformation was significantly increased. This result indicates that the potential risk of carcinogenicity from HQ is largely dependent upon the presence of promoter. Exposure of 50 ${\mu}M$ HQ increased the time-dependent apoptosis as measured by the ELISA kit. This concentration coincides with a dose of neoplastic transformation, indicating a possible link between apoptosis and HQ-induced cellular transformation. Hydroquinone generated Reactive Oxygen Species (ROS) which was evidenced by the treatment of antioxidants such as trolox and N-acetyl cysteine and the GSH depleting agent, BSO. Antioxidants blocked the generation of ROS and the GSH depleting agent, BSO dramatically increased the ROS production. Since HQ is known to increase ROS production thru activation of transcriptional factor such as c-Myb and Pim-1, it is speculated that ROS generation by HQ plays a role in the activation of oncogene, which may lead to neoplastic transformation. In addition, ROS is involved in the alteration of signal transduction, which regulates the apoptosis in many cellular systems. Thus, ROS-mediated apoptosis may be involved in the HQ-induced carcinogenic processes. Protein kinase C (PKC) is known to play pivotal roles in neoplastic transformation of cells and its high expression is often found in a variety of types of tumors including oral cancer. PKC translocation of PKC-${\alpha}$ was observed following HQ exposure. Altered signaling system may also play a role in the transformation process. Taken together, HQ leached from the dental resin does not pose a significant threat as a cancer causing agent, but its carcinogenic potential can be significantly elevated in the presence of promoter. The mechanism of HQ-induced carcinogenesis involved ROS generation, apoptosis and altered signaling pathway. The present study will provide a valuable data to estimate the potential risk of HQ as a carcinogen and understand mechanism of HQ-induced carcinogenesis in human epithelial cells.

A study on cytotoxicity of Ti-Nb alloys (Ti-Nb계 합금의 세포독성에 관한 연구)

  • Park, Hyo-Byeong
    • Journal of Technologic Dentistry
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    • v.25 no.1
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    • pp.89-94
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    • 2003
  • The use of titanium alloys as biomaterials is increasing due to their superior biocompatibility and enhanced corrosion resistance compared to conventional stainless steels and cobalt-based alloys. Ti-6Al-4V ($\alpha+\beta$type) alloy instead of pure titanium ($\alpha$type) is being widely used as biomaterials has some characteristics such as high fatigue strength, tensile strength and corrosion resistance. It also has similar characteristics to Ti in inducing bony ingrowth. But it has been reported recently that the vanadium element expresses cytotoxicity and carcinogenicity and the aluminium element is related with dementia of Alzheimer type and neurotoxicity. In order to overcome their detrimental effects, $\beta$-phase stabilizer Nb was chosen in the present study. CP-Ti(ASTM grade 2), Ti-3wt.%Nb($\alpha$type), Ti-20wt.%Nb ($\alpha+\beta$type) and Ti-40 wt.%Nb($\beta$type) alloys were melted by vacuum arc furnace. Biocompatibility of Ti-Nb alloys was evaluated by cytotoxicity test. The results can be summarized as follows: 1. For the cytotoxicity test, Ti-Nb alloys showed excellent biocompatibility compared to CP-Ti(ASTM grade 2), 316L STS and Co-Cr alloys.

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A Study on Classification and Management System for arcinogens (발암물질 분류 및 관리 체계 고찰)

  • Choi, Sang-Jun;Lim, Kyong-Che
    • Journal of the Korea Safety Management & Science
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    • v.12 no.3
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    • pp.107-119
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    • 2010
  • The aim of this study was to compare the carcinogen classification systems of developed countries or global organizations with domestic system under Industrial Safety and Health Act (ISHA). We selected the representative institutions which had carcinogen classification system such as International Agency for Research on Cancer (IARC), National Toxicological Program (NTP), Environmental Protection Agency (US-EPA), American Conference of Governmental Industrial Hygienists (ACGIH), and European Union (EU). We collected the carcinogen lists issued by 5 institutions, and merged by CAS number of each chemical with Microsoft Access 7.0. We found that confirmed human carcinogens, probable human carcinogens and possible human carcinogens were 34, 179, and 252, respectively. All of the institutions classified chemicals as 2 (NTP), 3 (EU) or 5 (IARC, ACGIH, US-EPA) categories based on the weight of scientific evidences for carcinogenicity and periodically updated the carcinogen list by regular procedure. However, a total of 90 chemicals could be classified as carcinogen under ISHA in Korea. There was no procedure or system which periodically update the carcinogen lists. In addition, the status of carcinogen classification according to regulation was confused. In conclusion, these findings suggest that the carcinogen classification and management system should be amended by consideration of systems of advanced institutions and the domestic regulation system.

A study on the provide of CMR substances information for Threshold Limit Values (TLVs) chemicals in KMoEL (노출기준 설정 화학물질의 CMR물질 정보 제공에 관한 연구)

  • Lee, Kwon Seob;Lee, Hye Jin;Lee, Jong Han
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.22 no.1
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    • pp.82-90
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    • 2012
  • Objectives: This study was performed to provide workplaces with political guidelines that apply international CMRs (Carcinogens, Mutagens, Reproductive toxins) information to Public Notice of TLVs (Threshold Limit Values). We analyzed information supply status about CMRs of international agencies and compared substances for which TLVs are set in KMoEL (Ministry of Employment and Labor in Korea). Methods: We referred to the reliable literature about classification criteria of CMRs corresponding to UN GHS (Globally Harmonized System of classification and Labeling of chemicals) and Public Notice No. 2009-68 'Standard for Classification, Labeling of Chemical Substance and Material Safety Data Sheet' in KMoEL. The classification system of CMRs in professional organizations (IARC, NTP, ACGIH, EU ECHA, KMoEL, etc.) was investigated through the internet and literature. Conclusions: 191 chemical substances among total 650 substances with TLVs are classified as carcinogens. Also, 43 substances classified as mutagens, and 44 as reproductive toxicants. These results suggest that the information of CMRs in Public Notice of TLV will be reorganized to 191 carcinogens, 43 mutagens, and 44 reproductive toxicants.

Toxicity Assessment and Establishment Acceptable Daily Intake of Lepimectin (레피멕틴(Lepimectin)의 독성평가와 일일섭취허용량 설정)

  • Jeong, Mi-Hye;Hong, Soon-Sung;Park, Kyung-Hun;Park, Jae-Eup;Kwack, Seung-Jun;Kim, Young-Bum;Han, Bum-Seok;Son, Woo-Chen
    • The Korean Journal of Pesticide Science
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    • v.15 no.2
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    • pp.218-229
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    • 2011
  • Lepimectin is a insecticide agent. In order to register this new pesticide, the series of toxicity data on animal testing were reviwed to evaluate its hazards to consumers and to determine its acceptable daily intake. Lepimectin was mostly excreted by feces. It has low acute oral toxicity while it has no dermal, ocular irritation and skin sensitization (As the result of subchronic, chronic toxicity and carcinogenicity showed changes of hematology and clinical biochemistry parameter of serum and blood.). Two-generation reproduction toxicity, genotoxicity, carcinogenicity and prenatal development toxicity were not proven. Therefore, the ADI for Lepimectin is 0.02 mg/kg/ bw/day, based on the NOAEL of 2.02 mg/kg/ bw/day of two-years carcinogenic toxicity study in rats and applying an uncertainty factor of 100.

Toxicity Assessment and Establishment Acceptable Daily Intake of Pyrimisulfan (피리미설판(Pyrimisulfan)의 독성평가와 일일섭취허용량 설정)

  • Jeong, Mi-Hye;Park, Kyung-Hun;Park, Jae-Eup;Kwack, Seung-Jon;Kim, Young-Bum;Han, Bum-Seok;Son, Woo-Chen
    • The Korean Journal of Pesticide Science
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    • v.15 no.2
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    • pp.208-217
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    • 2011
  • Pyrimisulfan is a herbicide. In order to register this new pesticide, the series of toxicity data on animal testing were reviewed to evaluate its hazards to consumers and also to determine its acceptable daily intake. Pyrimisulfan was excreted mostly by feces. It has low acute oral toxicity while it has no dermal, ocular irritation and skin sensitization (As the result of subchronic and chronic toxicity and carcinogenicity showed changes of hematology and liver.). Two-generation reproduction toxicity, genotoxicity, carcinogenicity and prenatal development toxicity were not proven. Therefore, the ADI for Pyrimisulfan is 0.1 mg/kg/ bw/day, based on the NOAEL of 10 mg/kg/ bw/day of 90-days repeated dose oral toxicity study in dogs while applying an uncertainty factor of 100.

Toxicity and Carcinogenicity of the Fusarium moniliforme MRC 826 Culture Material in Rats (랫드에서 Fusarium moniliforme MRC 826 배양물질의 독성 및 발암성에 관한 연구)

  • 신동진;신광순;이영순
    • Journal of Food Hygiene and Safety
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    • v.8 no.1
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    • pp.37-53
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    • 1993
  • F. moniliforme MRC 826, a common fungal contaminant of com, has been known to produce a group of mycotoxins, the fumonisins. By thin layer chromatography, fumonisin $B_{1}$ was detected in the F. moniliforme MRC 826 com culture material(CM) extracts. This study was performed to compare the toxicity and carcinogenicity of F. moniliforme MRC 826 CM with those of aflatoxin $B_1(AFB_1)$ in rats. The toxicity was tested over a period of 7 days in ten female Sprague-Dawley (SD) rats. Treatment group were fed a 1 : 1 mixture(wt/wt) of ground CM and basal diet in powder form, while other negative control group were given basal diet alone. The principal pathological changes in rats treated with 50% CM were hepatocellular hydropic degeneration and renal tubular necrosis. The cancer-promoting activity of CM was evaluated in the rat liver diethylnitrosamine-two thirds partial hepatectomy(DEN-PH) model for carcinogenesis. 70 male SO rats(ca. 170 g) were randomized into 5 groups. Group I served as the positive controls and received the basal diet containing 2 ppm $AFB_{1}$ group 2 received 5% CM, group 3 received 2.5% CM, group 4 received 5% normal com and group 5 received 2.5% normal com. 5% treated group showed cancer promoting activity in rat liver using DEN as initiator and the induction of glutathione S-transferase placental form positive foci as an end point after 6 weeks of promotion.

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A Cancer Risk Assessment of Di (2- ethylhexyl ) -phthalate - Application of MOE (Margin of Exposure) Approach (Di(2-ethylhexyl)phthalate의 발암위해성평가 - MOE(Margin of Exposure) 방법론의 활용 -)

  • 최시내;이효민;윤은경;서경원;김효정;박종세
    • Toxicological Research
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    • v.18 no.1
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    • pp.99-106
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    • 2002
  • The United States Environmental Protection Agency (EPA) characterized the cancer hazard of di(2-ethylhexyl)-phthalate (DEHP) as a B2 group (probable human carcinogen) and proposed "Guide-lines for Carcinogen Risk Assessment". This guidelines proposed alternative methods for analyzing carcinogen dose-response data and for extrapolating the effects of observed at high dose to predict that might occur at lower doses relevant to human exposure. This proposed guidelines state that "If in a particular case, the evidence indicated a threshold, as in the case of carcinogenicity being secondary to another toxicity that has a threshold, the margin of exposure analysis for toxicity is the same as is done for a non-cancer endpoint". DEHP is excellent candidate for reconideration under the new guidelines for carcinogen risk assessment (John Doull et al., 1998). This study is conducted about risk assessment for infant exposure on DEHP in powdered milk wing methodology in EPA's new guideline on carcinogenic risk assessment. Estimated cancer risk of DEHP in powdered milk and cow milk is 2.83$\times$$10^5$ (using cancer potency: 1.4$\times$$10^2$/ (mg/kg/day)) as mean and MOE is 12075 (using selected NOEL 20 mg/kg/day) as mean. mg/kg/day) as mean.

Studies on DNA Single Strand Break of Seven Phthalate Analogues in Mouse Lymphoma L5178Y Cells

  • Ryu, Jae-Chun;Kim, Hyung-Tae;Kim, Youn-Jung
    • Environmental Mutagens and Carcinogens
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    • v.22 no.3
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    • pp.164-168
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    • 2002
  • Phthalate analogues are a plasticizer and solvent used in industry and were reported to be a potential carcinogen classified in the category of suspected endocrine disruptors. Most common human exposure to these compounds may occur with contaminated food. They may migrate into food from plastic wrap or may enter food from general environmental contamination. 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 phthalates that possibly threaten the public health. To determine whether seven phthalate analogues i.e. diallyl phthalate, diisodecyl phthalate, di-n-nonyl phthalate, butyl benzyl phthalate, di-n-octyl phthalate, di-tridecyl phthalate, and dibutyl phthalate, can induce DNA strand breakage that is one of the various factors related to the mechanism of carcinogenicity, the comet assay which has been widely used for the detection and measurement of DNA strand breaks, was conducted in L5178Y mouse lymphoma cells. From these results, seven phthalates revealed dose-dependent decrease of cell viability, however, no remarkable cytotoxicity was observed even at high concentration of 100 $\mu\textrm{g}$/$m\ell$ phthalates. And also, the results showed that the induction of DNA strand breaks by seven phthalates was not significantly different from the control in this study.

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THE STUDY ON CARCINOGENICITY OF COPTIS RHIZOME AND CROTON TIGLIUM L.

  • Kang, Kyung-Sun;Cho, Jae-Jin;Kim, Bae-Hwan;Kim, Hyung-Ook;Shin, Dong-Jin;Lee, Yong-Soon;Lim, Yoon-Kyu
    • Toxicological Research
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    • v.8 no.1
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    • pp.131-137
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    • 1992
  • Sprague-Dawley rats aged six weeks divided into four groups and group 1, 2, 3 and 4 of rats were given an intrapertioneal injection of diethylnitrosamine at 200 mg/kg body weight. Group 4 was Control. Two weeks after beginning of the experiment, group 1 of rats were begun to feed on water containing 0.05% phenobarbital sodium as a promoter for six weeks, and CP-2 were intrapertioneally given to rats of group 2(20mg/kg) and group 3(1mg/kg). Three weeks after beginning of the experiment, partial hepatectomy was performed in all rats. Preneoplastic foci were identified histopathologically by glutathione S-transferase placental form (GST-P) activity. In the Immunohistochemical quantitative analysis of carcinogen-induced foci, it was concluded that CP-2 was not carcinogen.

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