• Proceedings of the Korean Society of Toxicology Conference
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• 2002.05a
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• pp.100-100
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• 2002

2-amino-3-methylimidazo[4,5-f]quinoline (IQ), a heterocyclic amine, significantly inhibits nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated macrophages. The decrease in NO production was found to correlate well with a decrease in iNOS mRNA expression as demonstrated by Northern blot analysis.(omitted)

• Preventive Nutrition and Food Science
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• v.6 no.1
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• pp.57-61
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• 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).

• Korean Journal of Food Science and Technology
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• v.28 no.4
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• pp.796-799
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• 1996

The antimutagenic properties of twenty-one strains of Bifidobacterium were examined using Salmonella typhimurium TA98 in an in vitro assay system. The mutagens utilized for testing included Trp-P-1 (3-amino-1, 4-dimethyl-$^{5}H-pyrido$ (4, 3-b) indole), benzopyrene, IQ (2-amino -3-methylimidazo [4,5-f] quinoline), and NQO. The lyophilized cells of strain showed inhibitory effect of 64, 38, 29 and 20% in average against Trp-P-1, benzopyrene, NQO and IQ, respectively. There was no marked variation between each strain or growth stage in the degree of antimutagenicity against Trp-P-1, benzopyrene and IQ. Twelve hour grown cells showed higher antimutagenicity against NQO than 5-day grown cells. The results indicate that Bifidobacterium cells had a antimutagenic effect against several well-known mutagens to some degree.

• Applied Biological Chemistry
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• v.38 no.5
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• pp.468-472
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• 1995

Substantial amount of caryophyllene oxide (CPO) is present in the essential oils of traditionally-used folk medicinal plants and herbal spices. The CPO, produced via chemical and/or enzymatic reaction of caryophyllene (CP), has largely being used as a flavoring component and exhibited a variety of biological activities. Now, we report the antimutagenic activity of CPO determined by Ames's preincubation test. S-9 fraction was prepared from the liver of rats treated with Arochor 1254. Anatoxin $B_1\;(AFB_1)$ and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) were used as mutagens. Reduction of mutagenicity of $AFB_1$ or IQ for S. typhimurium TA98 and TA100 by CPO was found to be a dose-dependant manner. CPO (500 ${\mu}g/plate$) reduced mutagenicity of AEB1 for S. typhimurium TA98 and TA100 to 89% and 71%, respectively. For IQ, similar results were observed against S. typhimurium TA98 and TA100, resulting in the inhibition percentage of 77% and 51%, respectively. CP also reduced mutagenicity of AEB1 and IQ for S. typhimurium TA98 and TA100, but the reduction rate was somewhat lowered relative to that of CPO. These results indicate that CPO could be developed as a potent antimutagenic flavoring agent.

• Environmental Mutagens and Carcinogens
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• v.18 no.1
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• pp.26-31
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• 1998

Antimutagenic activity of Saururus chinesis (Lour.) Bail was investigated for food-borne mutagens using S. typhimurium TA98. Methanol extract from Saururus Chinesis (Lour.) Bail was fractionated into hexane, chloroform, ethylacetate and butanol fractions, followed by determination of antimutagenic activity for food-borne mutagenic heterogenic amines (HCA). The hexane fraction exhibited a strong antimutagenic activity for 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQ), 2-amino-3,4-dimethyl-3H-imidazo[4,5-f]quinoline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 3-amino-1-methyl-5H-pyroid[4,3-b]indole acetate (Trp-2-A); however its fraction rather enhanced the bacterial mutagenicity of 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinozaline (4,8-diMeIQx) and 2-amino-3,7,8-trimethyl-3H-imidazo[4,5-f]quinoxline (7,8-diMeIQx). Active principle in the fraction was found to be two major compounds (${\gamma}$-crene B and epi-bicyclosesquiphellandrane) and 6 minor compounds (${\delta}$-caryophyllene, ${\gamma}$-elemene, ${\beta}$-cabebene, ${\delta}$-cadinene, ${\delta}$-selinene, and patchoulene). Modulation effect for the mutagenic activity of the food-borne mutagenic HCA by the fraction might be derived from a cumulative effect of each individual compounds. Hence, this hexane fraction might be use to reduce the production of mutagenic HCA during cooking process of protein-rich foods.

• Journal of the Korean Society of Food Science and Nutrition
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• v.26 no.1
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• pp.67-71
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• 1997

Different concentrations of lignin and hemicellulose were preincubated with 0.01$\mu\textrm{g}$ of 2-amino-3-methylimidazo［4, 5-f］quinoline(IQ) at simulated gastrointestinal pH condition s. The Ames Salmonella assay using Salmonella typhimurim TA98 was performed to detect any changes in the mutagenicity of IQ in the presence of lignin or hemicellulose. IQ revealed very weak or no mutagenicity when it was preincubated at pH 2.1. However, there was a dose-dependent inhibition of IQ mutagenicity in tile presence of lignin or hemicellulose at pH 5.4 and 6.6. The antimutagenic activities of fibers were not different from each other. Also, at lower concentrations of fibers, pH 5.4 was more effective in suppressing IQ mutagenicity, while 300$\mu\textrm{g}$ of lignin or hemicellulose significantly reduced the mutagenicity of IQ regardless of pH conditions. These results suggest that at gastrointestinal pH conditions, both soluble and insoluble fibers inhibit mutagenicity of IQ by adsorption. Therefore, a possible mechanism for Protective effect of fibers against cancer is due to their adsorption to mutagens in the gastrointestinal tract, and pH seems to be an important factor in the regulation of interactions between the fiber and mutagens.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.48-49
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• 2001

The carcinogens 2-amino-3-methylimidazo［4, 5-f］quinoline (IQ) and 1, 2-dimethylhydrazine (DMH) induce colon tumors in the Fisher 344 rat that contain mutations in Ctnnbl, the gene for b-catenin, but the pattern of mutation differs from that found in human colon cancers. In both species, mutations affect the glycogen synthase kinase 3$\beta$ (GSK-3$\beta$) consensus region of $\beta$-catenin, but whereas they directly substitute critical Ser/Thr phosphorylation sites in human colon cancers, the majority of mutations cluster around Ser$_{33}$ in the rat tumors.(omitted)d)

• Archives of Pharmacal Research
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• v.21 no.4
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• pp.363-369
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• 1998

Glutathione S-transferase placental form (GST-P) positive foci development and its expression in liver exposed by nongenotoxic carcinogens phenobarbital (PB) and clofibrate (CF), and genotoxic carcinogen 2-amino-3-methylimidazo[4,5-f] quinoline (IQ) were investigated as a measure of carcinogenic potential of these chemicals. Male F344 rats were initially given a single intraperitioneal injection of diethyinitrosamine (200 mg/kg), and 2 weeks later, animals were fed diets containing 0.03% IQ or 0.5% CF or 0.05% PB or basal diet as a control for 6 weeks. All rats were subjected to two-thirds partial hepatectomy (PH) at week 3. Sequential sacrifice of rats was performed at 8 weeks or 52 weeks, and liver tissues were examined for immunohistochemical staining of GST-P positive foci. The numbers (No./$cm^2$) and areas ($mm^2$/ $cm^2$) of GST-P positive foci were increased by IQ or PB, but were decreased by CF compare to the control. Consistent with the development of GST-P positive foci, a time-related increase in the expression of GST-P mRNA was found in the rats treated with IQ, whereas CF decreased it. The incidence of hepatocellular carcinoma at 52 weeks was increased by all three chemicals. These results show that PB and IQ induced GST-P positive foci, but the peroxisome proliferator CF did not, which suggest that the prediction of carcinogenic potency based on the development of prenoplastic foci may cause false negative in a particular category compounds like peroxisome proliferators.

• Environmental Mutagens and Carcinogens
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• v.19 no.2
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• pp.89-94
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• 1999

Cell proliferation and c-Jun expression pattern in liver exposed by nongenotoxic carcinogens phenobarbital (PB) and clofibrate, and genotoxic carcinogen 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) were investigated to see whether differential effects of genotoxic and non-genotoxic carcinogens on the development of neoplastic foci may be related to differential effect on cell proliferation. Male F344 rats were initially given a single intraperitioneal injection of diethylnitrosamine (200 mg/kg body weight), and 2 weeks later, animals were fed diets containing 0.03% IQ or 0.5% CE or 0.05% PB or basal diet as a control for 6 weeks. All rats were subjected to the two-thirds partial hepatectomy (PH) at week 3. Sequential sacrifice of rats was performed until 8 weeks. Cell proliferation was examined by immunohistochemical staining of bromodeoxyuridine and c-Jun expression was determined by northern blotting. The increase of cell proliferation rate after PH was significant in the rats fed 0.05% IQ and continued until 8 weeks, while the increase was not significant in the rats fed phenobarbital and clofibrate compared to that in the rats fed control diet. mRNA level of c-Jun in the liver treated with IQ was about 7 fold higher than that of control and peak at 5 hours after rH. In the liver treated with CE, mRNA level of c-Jun was 3-4 fold higher than that of control and the highest level of mRNA of c-Jun was seen at 24 hours after PH. These results show that differential effects of genotoxic and non-genotoxic carcinogens on the development of neoplastic foci may be related to differential effect on cell proliferation pattern.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.6
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• pp.986-993
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• 2002

Mushroom mycelia-cultured traditional meju (MTM) was prepared by inoculating 10% submerged-liquid culture of mushroom strains to five holes (1$\times$3 cm) per side of the traditionally-fermented meiu (10$\times$10$\times$10cm), followed by incubating additional 4 weeks at $25^{\circ}C$. Mushroom strains used were Neutari (Pleurotus ostreatus, PO), Yeongji (Ganoderma lucidum, GL), Synryeong (Agaricus blazei, AB), Ypsae (Grifola frondosa, GF), Pyogo(Lentinus edodes, PE), Dongchunghacho (Paecilomyces japonicus, PJ) and Sanghwang (Phellinus linteus PL). All MTMs showed an enhanced anticarcinogenicity against S-180 cell-induced mouse ascites cancer antimutagenicity against aflatoxin B$_1$ (AFB$_1$) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), and sensory qualities, relative to control meju. Such positive effects of MTM prepared with Sanghwang, Yeongji, or Synryeong were superior to those of MTM with Ypsae, Pyogo, Dongchunghacho, or Neutari.