• Title/Summary/Keyword: Metabolic activation

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Dual roles of estrogen metabolism in mammary carcinogenesis

  • Chang, Min-Sun
    • BMB Reports
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    • v.44 no.7
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    • pp.423-434
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    • 2011
  • A female hormone, estrogen, is linked to breast cancer incidence. Estrogens undergo phase I and II metabolism by which they are biotransformed into genotoxic catechol estrogen metabolites and conjugate metabolites are produced for excretion or accumulation. The molecular mechanisms underlying estrogen-mediated mammary carcinogenesis remain unclear. Cell proliferation through activation of estrogen receptor (ER) by its agonist ligands and is clearly considered as one of carcinogenic mechanisms. Recent studies have proposed that reactive oxygen species generated from estrogen or estrogen metabolites are attributed to genotoxic effects and signal transduction through influencing redox sensitive transcription factors resulting in cell transformation, cell cycle, migration, and invasion of the breast cancer. Conjuguation metabolic pathway is thought to protect cells from genotoxic and cytotoxic effects by catechol estrogen metabolites. However, methoxylated catechol estrogens have been shown to induce ER-mediated signaling pathways, implying that conjugation is not a simply detoxification pathway. Dual action of catechol estrogen metabolites in mammary carcinogenesis as the ER-signaling molecules and chemical carcinogen will be discussed in this review.

Evaluation of the Genetic Toxicity of Synthetic Chemical (XVIII)-in vitro Mouse Lymphoma Assay and in vivo Supravital Micronucleus Assay with Butylated Hydroxytoluene (BHT)

  • Kim, Youn-Jung;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.3 no.3
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    • pp.172-176
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    • 2007
  • Butylated hydroxytoluene (BHT) is widely used antioxidant food additives. It has been extensively studied for potential toxicities. BHT appears adverse effects in liver and thyroid. In this study, we evaluated the genetic toxicity of BHT with more advanced methods, in vitro mouse lymphoma assay $tk^{+/-}$ gene assay (MLA) and in vivo mouse supravital micronucleus (MN) assay. BHT did not appear the significantly results in the absence and presence of metabolic activation system with MLA. Also, in vivo testing of BHT yielded negative results with supravital MN assay. These results suggest that BHT itself was not generally considered genotoxic.

Genotoxicological safety of the Gamma-Irradiated Medicinal Herbs in the Micronucleus Test Using CHO Cells In Vitro (CHO 세포에서의 소핵시험을 이용한 감마선조사 생약재의 안전성에 관한 유전독성학적 평가)

  • 조성기
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.26 no.5
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    • pp.952-957
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    • 1997
  • The three medicinal herbs-Curcuman longa Linne, Paeonia japonica Miyabe, Scutellaria baikalensis George-irradiated with gamma rays were tested for their possible genotoxicity. The methanol-soluble and water-soluble fractions of the 10kGy gamma-irradiated herbs were examined in cultured Chinese hamster ovary(CHO) cells for their ability to induce micronuclei. No mutagenicity of each test material was detected in the assay with or without metabolic activation. The safety of the herbs irradiated with gamma rays at practical doses needs further investigations using in vivo genotoxicity and chronic and reproductive toxicity tests.

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Genotoxicological Safety of the Gamma Irradiated Medicinal Herbs in the salmonella typhimurium Reversion Assay (복귀돌연변이시험을 이용한 감마선조사 생약재의 안전성에 관한 유전독성학적 평가)

  • 조성기;육홍선;변명우
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.26 no.5
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    • pp.958-964
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    • 1997
  • The three medicinal herbs-Curcuma longa Linne, Paeonia japonica Miyabe, Scutellaria baikalensis George-irradiated with gamma rays have been tested for their possible genotoxicity. The methanol-soluble and water-soluble fractions of the 10kGy gamma-iradiated herbs were examined in the Salmonella typhimurium histidine reversion assy(Ames test) using S. typhimurium TA98, TA100 and TA102 as tester strains. No mutabenicity was detected in this assay with or without metabolic activation. The safety of the herbs irradiated with gamma rays at practical doses needs to be evaluated in further tests of genotoxicity in vivo and chronic and reproductive toxicity.

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Genotoxicological Safety of the Gamma-Irradiated Korean Red Ginseng In vitro (감마선 조사 홍삼의 안전성에 관한 유전독성학적 연구)

  • 조성기;육홍선;변명우
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.25 no.3
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    • pp.491-496
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    • 1996
  • This experiment was performed to determine the safety of the Korean red ginseng irradiated with gamma rays with respect to genotoxicity. Ethanol extracts of the 5 and 10 kGy gamma-irradiated red ginseng were examined in two short-term in vitro tests : (1) Salmonella typhimurium reversion assay(Ames test) in strain TA 98, TA 100 and TA 102 (2) Micronucleus test in cultured Chinese hamster ovary(CHO) cells. No mutagenicity was detected in the two assays with or without metabolic activation. It was suggested that the Korean red ginseng irradiated with gamma rays did not cause genotoxicity in vitro. Further tests of genotoxicity in vivo, chronic and reproductive toxicity should be carried out to determine whether it is safe to irradiate Korean red ginseng with practical doses of gamma rays.

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Genotoxicity Study of CJ-11555 (CJ-11555의 유전독성에 관한 연구)

  • 박지은;이성학;최재묵;김일환;김덕열;노현정;김택로;김영훈;임지웅
    • Toxicological Research
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    • v.20 no.2
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    • pp.153-158
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    • 2004
  • To evaluate the genotoxicity of CJ-11555, an anti-cirrhotic agent, the reverse mutation test, chromosomal aberration test and in vivo micronucleus test in rats were performed. In the reverse mutation test, the treatment of CJ-11555 at doses of 33.3, 100, 333, 1000, 3330 and 5000 $\mu\textrm{g}$/plate with and without 89 did not induce mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, TA1537, and Escherichia coli (E. call) WP2uvrA. In chromosomal aberration test, CJ-11555 did not induce structural a chromosomal aberration in Chinese hamster ovary (CHO) cells with and without metabolic activation at all doses. In micronucleus test, CJ-11555 did not induce any statistically significant increases in micronucleated polychromatic erythrocyte (MNPCE) at doses of 500, 1000, and 2000 mg/kg. These results suggest that CJ-11555 might not have a mutagenic potential under the conditions in this study.

Genotoxicological Safety of the Gamma-Irradiated Medicinal Herbs (감마선 조사 생약재의 안전성에 관한 유전독성학적 평가)

  • 조성기
    • Journal of Food Hygiene and Safety
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    • v.12 no.3
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    • pp.217-227
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    • 1997
  • These experiments were performed to investigate the safety of the three medicinal herbs- Curcuma longa Linne, Paeonia japonica Miyabe, Scutellaria baikalensis George-irradiated with gamma rays in respect of genotoxicity. The methanol-soluble and water-soluble fractions of the methanol-water extracts of the 10 kGy gamma-irradiated herbs were examined in two short-term in vitro tests : (1) Salmonella typhimurium reversion assay (Ames test) in strain TA 98, TA 100 and TA 012 (2) Micronucleus test in cultured Chinese hamster ovary (CHO) cells. No mutagenicity was detected in the assays with or without metabolic activation. From these results, the safety of the herbs irradiated with gamma rays at practical doses could be revealed in further tests of genotoxicity in vivo, chronic and reproductive toxiceity.

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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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    • v.4 no.2
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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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Studies on the Genetic Toxicity of NP-77A

  • Kim, Jai-Hyun;Cho, In-Koo;Park, Kun-Hyuck;Ha, Kwang-Won
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1995.04a
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    • pp.123-123
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    • 1995
  • To evaluate the genetic toxicity of NP-77A which is selected as the candidate of anti-HBV agent, we performed ames test, micronucleus test, and chromosome aberration test on the CHL cell in vitro. The Ames test was carried out with 5 fold diluted 5 concentrations from 25mg/plate using S. typhimurium and E.coli. After 48hrs incubation, revertant colony numbers was calculated with and without metabolic activation system. In vivo micronucleus test, we investigated the rate of the occurrence of micronucleus after I.P. administration to mice. Andalso, we observed the incidence rate of cells with chromosomal aberration by NP-77A treatment using CHL cell line.

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Evaluation of the Genetic Toxicity of Synthetic Chemical (XVII) -In vitro Mouse Lymphoma Assay and In vitro Supravital Micronucleus Assay with 1, 2-Dichlorobenzene

  • Kim, Youn-Jung;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.3 no.2
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    • pp.113-118
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    • 2007
  • Chlorobenzenes due to their acute toxicity and the capability of bioaccumulating are of great health and environmental concern. Especially, 1, 2-dichlorobenzene (CAS No. 95-50-1) is used for organic synthesis, dye manufacture, as a solvent and for other applications in chemical industry. Adverse effects of 1, 2-dichlorobenzene includes increases in liver and kidney weights and hepatotoxicity. In this study, we evaluated the genetic toxicity of 1, 2-dichlorobenzene with more advanced methods, in vitro mouse lymphoma assay $tk^{+/-}$ gene assay (MLA) and in vitro mouse supravital micronucleus (MN) assay. 1, 2-Dichlorobenzene appeared the significantly positive results and the induction of large mutant colonies only in the presence of metabolic activation system with MLA. But in vitro testing of 1, 2-dichlorobenzene yielded negative results with supravital MN assay. These results suggest that 1, 2-dichlorobenzene may play a mutagen rather than clastogen in vitro mammalian system.