• 한국환경성돌연변이발암원학회지
• /
• 제22권4호
• /
• pp.259-265
• /
• 2002

Phthalate analogues are a plasticizer and solvent used in industry. Phthalates 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. Concern about their use has been mounting. To screen and elucidate the endocrine disrupting activity and their mechanism of phthalate analogues, first of all, E-screen assay was performed in MCF7 human breast cancer cells with seven phthalate analogues. In this cell proliferation assay, only dibutyl phthalate (DBP) showed weak estrogenic activity. Also the yeast-based transcription assay to assess the interactions of DBP with the estrogen, androgen, and progesterone receptors was conducted. DBP in the concentration ranges from 10$^{-16}$ to 10$^{-11}$ M was active in the estrogen transcriptional assay, but it did not show the effect on $\beta$-galactosidase activity in the progesterone and androgen transcriptional assays. These data indicate that DBP shows estrogenic potential and can be classified as weak and/or suspected endocrine disrupting chemicals.

• Preventive Nutrition and Food Science
• /
• 제6권1호
• /
• pp.57-61
• /
• 2001

Conjugated linoleic acid (CLA), when incorporated into mouse liver microsomal membranes, selectively inhibits the mutagenesis of 2-amino-3-methylimidazo[4,5-f] quinoline (IQ). Nine-week old female ICR mice were given (p.o.) 0.1 mL olive oil alone (control), 0.1 mL olive oil plus 0.1 mL linoleic acid, or 0.1 mL olive oil plus 0.1 mL CLA, twice weekly for four weeks. The animals were then sacrificed and liver S-9 fractions were prepared. Activation of IQ for mutagenesis by the liver S-9 from CLA-treated mice was significantly reduced in comparison wit liver S-9 from control or linolic acid-treated mice. By contrast, the activation of 7,12-dimethylbenz[a] anthracene (DMBA) and benzo[a] pyrene (BP) was unaffected. Hence, CLA incorporated into phospholipids may selectively affect cytochrome P450 isozymes responsible for activating IQ, but not those which activate BP or DMBA. The addition of free CLA or the methyl esters of CLA, linoleic acid, or oleic acid, to control S-9 inhibited the activation of all three mutagens (IQ, BP, and DMBA).

• Journal of Microbiology and Biotechnology
• /
• 제22권6호
• /
• pp.838-848
• /
• 2012

Orally administered herbal glycosides are metabolized to their hydrophobic compounds by intestinal microflora in the intestine of animals and human, not liver enzymes, and absorbed from the intestine to the blood. Of these metabolites, some, such as quercetin and kaempherol, are mutagenic. The fecal bacterial enzyme fraction (fecalase) of human or animals has been used for measuring the mutagenicity of dietary glycosides. However, the fecalase activity between individuals is significantly different and its preparation is laborious and odious. Therefore, we developed a fecal microbial enzyme mix (FM) usable in the Ames test to remediate the fluctuated reaction system activating natural glycosides to mutagens. We selected, cultured, and mixed 4 bacteria highly producing glycosidase activities based on a cell-free extract of feces (fecalase) from 100 healthy Korean volunteers. When the mutagenicities of rutin and methanol extract of the flos of Sophora japonica L. (SFME), of which the major constituent is rutin, towards Salmonella typhimurium strains TA 98, 100, 102, 1,535, and 1,537 were tested using FM and/or S9 mix, these agents were potently mutagenic. These mutagenicities using FM were not significantly different compared with those using Korean fecalase. SFME and rutin were potently mutagenic in the test when these were treated with fecalase or FM in the presence of S9 mix, followed by those treated with S9 mix alone and those with fecalase or FM. Freeze-dried FM was more stable in storage than fecalase. Based on these findings, FM could be usable instead of human fecalase in the Ames test.

• 한국축산식품학회지
• /
• 제31권4호
• /
• pp.563-569
• /
• 2011

일상 생활에서 섭취하는 가열한 생선, 육류 등의 고단백질 식품에서는 돌연변이원, 발암가능성 물질인 heterocyclic amine류가 생성된다. 안전성 측면을 고려하고자 백련 잎을 이용한 마리네이드 소스를 첨가하여 쇠고기의 HCAs의 형성억제효과와 돌연변이원성 억제효과를 알아보았다. Ames assay 결과 백련 잎 butanol fraction을 2.0 g 첨가하여 가열한 쇠고기 스테이크에서 61.5%로 높은 돌연변이원성 억제효과를 나타내었지만 용매 별 fraction 첨가군 사이에서는 유의적인 차이를 나타내지 않았다. 가열 전 쇠고기 마리네이드 소스에 식용이 가능한 백련잎 water fraction(2.0, 4.0, 8.0 g)을 첨가한 후 $190^{\circ}C$에서 가열한 결과 MeIQx(2-amino-3,8 dimethylimidazo[4,5-f]-quinoxalin)는 30.9-63.5%, PhIP(2-amino-1-methyl-6-pheny-limidazo[4,5-b]-pyridine)는 31.6-60.7% 억제되었다. $225^{\circ}C$에서의 가열된 쇠고기에서는 MeIQx가 38.1-65.3%, DiMeIQx (2-amino-3,4,8 trimethylimidazo[4,5-f]-quinoxaline)는 36.8-73.9%, PhIP는 33.9- 67.6%의 억제효과를 보였다. 따라서 백련 잎 추출물은 heterocyclic amine류 형성과 돌연변이 원성을 억제하는 효과가 있는 것으로 나타나 고단백질 식품 섭취시 안전성 측면에서 긍정적인 영향을 미칠 것으로 판단된다.

• 한국식품과학회지
• /
• 제26권2호
• /
• pp.188-194
• /
• 1994

쌀의 돌연변이 억제초과를 검토하기 위해 여러 돌연변이 유발원(3-amino-1,4-dimethyl-5H-pyrido [4,3-b]indole(Trp-P-1), 3-amino-1-methyl-5H-pyrido [4,3-b]indole(Trp-P-2), sodium azide(SA), 2-nitrofluorene(2NF), mitomycin C(MMC), aflatoxin $B_1(AFB_1)$ 및 4-nitroquinoline oxide(4-NQO))에 대한 쌀 추출물들의 억제효과를 Salmonella typhimurium reversion assay, SOS chromotest 및 spore rec-assay로 조사하였다. S. typhimurium TA 98 및 TA 100을 이용한 Salmonella typhimurium reversion assay에서 현미(일품벼) 메탄올 추출물이 핵산, 클로로포름 및 물 추출물 보다 억제효과가 크게 나타났다. 메탄올 추출물의 경우, 간접변이원(Trp-P-1, Trp-P-2 및 $AFB_1$)에 대한 억제효과가 약 85% 이상으로써, 직접변이원(4-NQO, 2NF)에 대한 효과 보다 크게 나타났다. 메탄올 추출물은 E. coli PQ37을 이용한 SOS chromotest에서도 Trp-P-1, Trp-P-2, $AFB_1$ 및 4-NQO에 의한 SOS유도에 대해 $77.6{\sim}88.9%$의 억제작용을 나타내었고, B. subtilis $H17(rec^+)$과 $M45(rec^-)$를 사용한 spore recassay에서도 양성대조구인 $AFB_1$ 및 MMC에 의한 저지대의 차이를 감소시켜 억제작용을 나타내었다. 현미(일품벼)의 메탄올 추출물은 농도가 증가함에 따라 돌연변이 억제효과가 증가하였으나, 농도가 5 mg/plate(5%) 이상에서는 억제효과가 약 90%로 일정하였다. 쌀 품종별 메탄올 추출물의 억제효과는 조사된 11개 품종 모두에게서 나타나, 직접변이원인 2NF에 대해 $4.1{\sim}75.2%$의 억제를, 간접 변이원인 Trp-P-1에 대해 $99.5{\sim}100.2%$의 억제를 나타내었다. 백미와 현미(일품벼)간의 돌연변이 억제효과를 비교해 볼 경우, Trp-P-1 및 Trp-P-2에 의한 변이에 대해서는 차이가 없었으나(p>0.05), 4-NQO에 의한 변이에 대해서는 현미의 효과가 높았다(p<0.05).

• 한국환경성돌연변이발암원학회지
• /
• 제26권3호
• /
• pp.63-68
• /
• 2006

There are $10{\sim}30%$ polyphenol and $2{\sim}4%$ caffeine in green tea. Caffeine is a kind of alkaloid containing nitrogen which cause stimulation, impatience, headache, insomnia, low birth weight infant. Because of these negative effect, decaffeined beverage came out and decaffeined coffee already have a big market since 1970s. Having proving the physiologic functions of green tea, high consumption of coffee is shifting to green tea. Because of the carcinogenic effect of the organic solvents, decaffeine processing with supercritical carbon dioxide has industrialized and have an advantage in environment-friendly and minimized flavor loss. Decaffeined green tea using supercritical carbon dioxide is considered to be safe but there are not enough study, We investigated the chromosome aberration test with mammalian cell line, CHL. When the cells were treated with 5000, 2000, 1000 ${\mu}g/ml$ and compared with the negative controls, there were no significant (P>0.05) increased chromosome aberration. Same results was observed when adding S9 mixture or not. As a result, water extract of decaffeined green tea using supercritical carbon dioxide does not induce chromosome aberration.

• 한국환경성돌연변이발암원학회지
• /
• 제26권4호
• /
• pp.119-124
• /
• 2006

There are $10{\sim}30%$ polyphenol and $2{\sim}4%$ caffeine in green tea. Caffeine is a kind of alkaloid containing nitrogen which cause stimulation, impatience, headache, insomnia, low birth weight infant. Because of these negative effect, decaffeined beverage came out and decaffeined coffee already have a big market since 1970s. Having proving the physiologic functions of green tea, high consumption of coffee is shifting to green tea. Because of the carcinogenic effect of the organic solvents, decaffeine processing with supercritical carbon dioxide has industrialized and have an advantage in environment-friendly and minimized flavor loss. Decaffeined green tea using supercritical carbon dioxide is considered to be safe but there are not enough study. We investigated the chromosome aberration test with mammalian cell line, CHL. When the cells were treated with 5000, 2000, 1000 ${\mu}g/ml$ and compared with the negative controls, there were no significant(P>0.05) increased chromosome aberration. Same results was observed when adding S9 mixture or not. As a result, water extract of decaffeined green tea using supercritical carbon dioxide does not induce chromosome aberration.

• 한국환경성돌연변이발암원학회지
• /
• 제26권4호
• /
• pp.125-132
• /
• 2006

Previous studies showed that epigallocatechin gallate(EGCG) have substantial effects of suppressing the N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)-initiated cell transformation process on the bases of foci formation frequency and loss of anchorage dependency. In this study we tried to clarify the molecular mechanism of suppressing the cell transformation process. Mouse cell line balb/c 3T3 A31-1-1 was exposed 2 days to MNNG followed by 15 days 12-O-tetradecanoylphorbol-13-acetate(TPA) treatment for our transformation process. EGCG was added after the time point of 24 hours exposure to TPA and incubated for 19 days. 2029 genes were selected in our transformation process that showed fold change value of 1.5 or more in the microarray gene expression analysis covering the mouse full genome. These genes were found to be involved mainly in the cell cycle pathway, focal adhesion, adherens junction, TGE-$\beta$ signaling, apoptosis, lysine degradation, insulin signaling, ECM-receptor interaction. Among the genes, we focused on the 631 genes(FC>0.5) reciprocally affected by EGCG treatment. Our study suggest that EGCG down-regulate the gene expressions of up stream signaling factors such as nemo like kinase with MAPK activity and PI3-Kinase, Ras GTPase and down stream factors such as cyclin D1, D2, H, T2, cdk6.

• 한국환경성돌연변이발암원학회지
• /
• 제17권2호
• /
• pp.78-91
• /
• 1997

Peroxisome is a single membrane-bounded organelle found in hepatic parenchymal cells and kidney tubular epithelial cells. A number of enzymes exist in peroxisome contributing to anabolic and catabolic peroxisomal functions. Extramitochontriai $\beta$-oxidation of fatty acid is a major function of peroxisome. Peroxisomes can be proliferated by many structually unrelated compounds such as hypolipidemic drugs, plasticizers, pesticides, some pharmaceutical agents and high fat diet. These chemicals, called peroxisome proliferators, act via the peroxisome proliferator activated receptor, to induce peroxisome proliferation, hepatomegaly and hepatocellular carcinoma in rodent. The clear mechanisms of peroxisome proliferator-induced hepatocarcinogenesis have been not demonstrated. Since they are not genotoxic, biochemical changes or changes in gene expressions may be involved. A free radical theory has been suggested based on the finding of oxidative damages of macromolecules by hydrogen peroxide released in the peroxisomal $\beta$-oxidation of fatty acid. Increased cell proliferation by a peroxisome proliferator has been also thought to be an important factor in the hepatocarcinogenesis as suggested in other cases of nongenotoxic carcinogenesis. The alternation of eicosanoid concentrations by peroxisome proliferators may be important in the peroxisome proliferator-induced hepatocarcinogenesis since peroxisome proliferators decrease the concentration of eicosanoids, and the peroxisome proliferator ciprofibrate-eicosanoid combination is comitogenic and costimulates some mitogenic signals in hepatocytes. All of proposed mechanisms should be considered in the peroxisome prolifrator-induced hepatocarcinogenesis.

• 한국환경성돌연변이발암원학회지
• /
• 제21권2호
• /
• pp.113-117
• /
• 2001

The screening of various molecular descriptors for predicting carcinogenic, mutagenic and teratogenic activities of chlorinated aliphatic compounds as drinking water disinfection byproducts (DBPs) has been investigated for the application of quantitative structure-activity relationships (QSAR). The present work embodies the study of relationship between molecular descriptors and toxicity parameters of the genotoxicity endpoints for the screening of relevant molecular descriptors. The toxicity Indices for 29 compounds constituting the testing set were computed by the PASS program and active values were chosen. We investigate feasibility of screening descriptors and of their applications among different genotoxic endpoints. The correlation to teratogenicity of all 29 compounds was significantly improved when the same analysis was done with 20 alkanes only without alkene compounds. The HOMO (highest occupied molecular orbital) energy and number of Cl parameters were dominantly contributed.