• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9517-9522
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• 2014

Purple rice (Oryza sativa L. var. indica) cv. Kum Doisaket is cultivated in northern Thailand. This study evaluated the mutagenic and antimutagenic properties of hydrophilic and lipophilic components of purple rice using the Ames test. The seed and hull of purple rice were extracted with hexane, methanol, ethanol, and water. The methanol extracts had the highest amounts of phenolic acids and flavonoids, while the hexane extracts contained large amount of tocols and ${\gamma}$-oryzanol. None of the extracts were mutagenic in Salmonella typhimurium strains TA98 and TA100. The hexane extract of rice hull and the methanol extract of rice seed were strongly effective against aflatoxin B1- and 2-amino-3, 4 dimethylimidazo (4, 5-f) quinoline-induced mutagenesis, while aqueous extracts showed weakly antimutagenic properties. All extracts with the exception of aqueous extracts enhanced the number of revertant colonies from benzo (a) pyrene induced-mutagenesis. None of the extracts inhibited mutagenesis induced by the direct mutagens 2-(2-furyl)-3-(5-nitro-2-furyl)-acrylamide and sodium azide. The hull extracts showed more potent antimutagenicity than the seed extracts. Based on a chemical analysis, ${\gamma}$-oryzanol and ${\gamma}$-tocotrienol in the hull and cyanidin-3-glucoside and peonidin-3-glucoside in the seed are candidate antimutagens in purple rice. The antimutagenic mechanisms of purple rice might be related to either modulation of mutagen metabolizing enzymes or direct attack on electrophiles. These findings supported the use of Thai purple rice as a cancer chemopreventive agent.

• Biomedical Science Letters
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• v.12 no.4
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• pp.361-370
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• 2006

To evaluate an effect of pathological liver damage on the conjugation of cyclohexane metabolites, rats were pretreated with 50% $CCl_4$ dissolved in olive oil (0.1 ml/100 g body weight) 10 or 17 times intraperitoneally at intervals of every other day. On the basis of liver function, the animals pretreated with $CCl_4$ 10 times were identified as acutely liver damaged ones and the animals pretreated with $CCl_4$ 17 times were identified as severly liver damaged ones. To these liver damaged animals, cyclohexane (a single dose of 1.56 g/kg body weight, i.p.) was administered at 48 hr after the last injection of $CCl_4$. The rats were sacrificed at 4 or 8 hr after injection of cyclohexane. The cyclohexane metabolites, cyclohexanol (CH-ol), cyclohexane-1,2-diol (CH-1,2-diol), cyclohexane-1,4-diol (CH-1,4-diol), and their glucuronyl conjugates and cyclohexanone were detected in the urine of cyclohexane treated rats. The urinary concentration of cyclohexane metabolites was generally more increased in liver damaged animals than normal ones, and the increasing rate was higher in $CCl_4$ 17 times injected rats than 10 times injected ones. And liver damaged.ats, especially $CCl_4$ 17 times treated ones, had an enhanced ability of glucuronyl conjugation to CH-ol analogues compared with normal group. Futhermore, CH-1,2 and 1,4-diol were all conjugated with glucuronic acid in $CCl_4$ 17 times injected animals. On the other hand, the increasing rate of activities of hepatic cytochrome P450 dependent aniline hydroxylase, alcohol dehydrogenase and urine diphosphate glucuronyl transferase was higher in 17 times $CCl_4$-treated rats compared with normal and $CCl_4$ 10 times injected animals. Taken all together, it is assumed that an increased urinary excretion amount of cyclohexane metabolites in liver damaged rats might be caused by an increase in the activities of cyclohexane metabolizing enzymes. And enhanced conjugating ability of CH-ol in liver damaged animals and novel finding of conjugating form of CH-1,2 and 1,4-diol might be caused by increase in the activity of hepatic diphosphouridine glucuronyltransferase.

• Toxicological Research
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• v.11 no.2
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• pp.205-213
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• 1995

This study was undertaken to investigate the effects of organic solvents on xenobiotic metabollzing enzyme system in vivo by meaas of experimental conditions i.e. (1) single group which was treated by benzene (B), toluene (T) and xylene (X), respectively, (2) combination group which was treated by mixture of benzene+toluene (BT), benzene+xylene (BX), and toluene+xylene (TX), respectively, (3) mixture group which was treated by benzene+ toluene+xylene mixture (M), and to interpreat the interaction between the organic solvents metabolizing enzymes. 1. The contents of cytochrome P-450 in liver microsomes were increased (p < 0.01) in organic solvents treated groups, and the contents of cytochrome P-450 were increased by following order of B < T < M < BT=BX < X < TX. 2. The activity of cytochrome P-450 dependent AHHase was significantly higher in organic solvents treated groups than in control group (p < 0.01), and the activity of AHHase was increased by following order of B < T < BT=BX=TX=xylene < M. 3. The activity of NADPH P-450 reductase was significantly higher in organic solvents treated groups than in control group (p < 0.01), and the order of M < combinated group < X < T

• Molecular & Cellular Toxicology
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• v.2 no.2
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• pp.75-80
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• 2006

Biomarkers identify various stages and interactions on the pathway from exposure to disease. The three categories of biomarkers are those measuring susceptibility, exposure and effect. Susceptibility biomarkers are identifiable genetic variations affecting absorption, metabolism or response to environmental agents. Biomarkers of exposure indicate the amount of a foreign compound that is absorbed into the body. Biological measurements performed on human tissues are vastly expanding the capabilities of classical epidemiology, which has relied primarily on estimates of human exposure derived form chemical levels in the air, water, and other exposure routes. Biomarkers of exposure indicate the amount of a foreign compound that is absorbed into the body. Biological measurements performed on human tissues are vastly expanding the capabilities of classical epidemiology, which has relied primarily on estimates of human exposure derived form chemical levels in the air, water, and other exposure routes. The biomarker response is typical of chemical pollution by specific classes of compound, such as (i) heavy metals (mercury, cadmium, lead, zinc), responsible for the induction of metallothionein synthesis, and (ii) organochlorinated pollutants (PCBs, dioxins, DDT congeners) and polycyclic aromatic hydrocarbons (PAHs), which induce the mixed function oxygenase (MFO) involved in their bio transformations and elimination. Currently genomic researches are developed in human cDNA clone subarrays oriented toward the expression of genes involved in responses to xenobiotic metabolizing enzymes, cell cycle components, oncogenes, tumor suppressor genes, DNA repair genes, estrogen-responsive genes, oxidative stress genes, and genes known to be involved in apoptotic cell death. Several research laboratories in Korea for kicking off these Environmental Genomics were summarized.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3409-3416
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• 2012

Aim: It is well known that polycyclic aromatic hydrocarbons (PAHs) such as benzo (a) pyrene have carcinogenic properties and may cause many types of cancers in human populations. Genetic susceptibility might be due to variation in genes encoding for carcinogen metabolizing enzymes, such as cytochrome P-450 (CYP450). Our study aimed to investigate the effect of genetic polymorphisms of CYP1A1 (m1 and m2) on genetic damage in 115 coal-tar workers exposed to PAHs at their work place. Methods: Genetic polymorphisms of CYP1A1 were determined by the PCR-RFLP method. Comet and buccal micronucleus assays were used to evaluate genetic damage among 115 coal tar workers and 105 control subjects. Results: Both CYP1A1 m1 and CYP1A1 m2 heterozygous and homozygous (wt/mt+mt/mt) variants individually as well as synergistically showed significant association (P<0.05) with genetic damage as measured by tail moment (TM) and buccal micronuclei (BMN) frequencies in control and exposed subjects. Conclusion: In our study we found significant association of CYP1A1 m1 and m2 heterozygous (wt/mt)+homozygous (mt/mt) variants with genetic damage suggesting that these polymorphisms may modulate the effects of PAH exposure in occupational settings.

• The Korea Journal of Herbology
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• v.30 no.1
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• pp.51-57
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• 2015

Objectives : The effect of pear extract with Daekumeumjagami and vitamin C medication(PDV) on alcohol metabolism and hepatic injury was assessed following hepatic injury induced by alcohol in mice. Methods : The model of alcoholic hepatic injury was established by orally administration with 3 g/kg 25% alcohol in mice. PDV was orally administrated once a day for 5 days. Mice were randomly divided into 5 groups : normal group, control group, and PDV groups (PDV-A, PDV-B and PDV-C). The activities of aspartate amino transferase (AST) and alanine amino transferase (ALT) and alcohol dehydrogenase (ADH) in serum, superoxide dismutase (SOD) and catalase in liver were determined after alcohol exposure. Results : Compared with control group, treatment with PDV-B and PDV-C significantly elevated activities of ADH. Moreover, the index of hepatic injury in serum was significantly decreased by treatment with PDV-B and PDV-C in ALT activity and PDV-C in AST activity. Additionally, enhanced catalase activities in liver was found in PDV-C treated mice after exposure to alcohol. Also, WBC in blood was significantly lower by treatment with PDV-B and PDV-C. Conclusions : This study suggests that PDV treatment could enhance alcohol metabolism, and prevent hepatic injury after alcoholic hepatic injury and that this effect is likely related to its modulation on the alcohol metabolizing and antioxidant enzymes.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2002.10a
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• pp.171-171
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• 2002

Recent industrial society has human widely exposed to PAHs that are comming from the incomplete combustion of organic material as widerspread environmetal contaminants. Biological activities of PAHs are not known although PAHs are considered as carcinogens. PAHs in the mammalian cells affect CYP1A1 gene expression as well as other phase II drug metabolizing enzymes as UDPGT, NMOR etc. The mechanism of action of PAHs has been studied extensively, however it is not clear how PAHs turn on CYP1A1 in human breast cancer. Our labolatory have been studied the effect of PAHs in the human breast cancer cell lind MCF7. In this study, we examined the ZR-75-1 human breast cancer cells as a new system to evaluate bioactivity of PAHs. ZR-75-1 human breast cancer cell line has been estabilished from the breast cnacer patient, has estrogen receptors and progesteron receptors. We have been able to estbilish long term culture system of this cells then used for the study to observe the effect of PAHs. We demonstrate that PAHs induced the transcription of an aryl hydrocarbon-responsive reporter vector containing the CYP1A1 promoter and 7-ethoxyresolufin O-deethylase(EROD) activity of CYP1A1 enzyme in a concentration-dependant manner. RT-PCR analysises indicated that PAHs significantly up-regulate the constitutive level of CYP1A1 mRNA. Apparently, ZR-75-1 cells have Aryl hydrocarbon recetors, therefore it would be good experimental tool to study the cross-talk between PAHs and steroid actions.

• Journal of Society of Preventive Korean Medicine
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• v.7 no.2
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• pp.65-74
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• 2003

Objective : The aim of present study is to evaluate the inhibitory potential of licorice extract and glycyrrhizin on cytochrome P450(CYP) in human liver microsomes. Methods : Using human liver microsomes, water extract of licorice and glycyrrhizin as an inhibitor were co-incubated with each probe drug representing selective CYP isoform activity. We measured relative metabolic activity in incubation condition compared to that with no extract of licorice using HPLC system. Results : Both water extracts of licorice and glycyrrhizin showed inhibitory effect on CYP-catalyzed reactions. CYP2C19 $(IC_{50}=126.7{\mu}g/ml)$ is most potently inhibited by water extract than other tested CYP isoforms$(IC_{50}>450{\mu}g/ml)$, but glycyrrhizin exhibited potent inhibition on CYP1A2$(IC_{50}=106.9{\mu}g/ml)$ followed by CYP2C9 and CYP2D6. Conclusion: These results indicate that water extract of licorice and glycyrrhizin have inhibitory potential on CYP-catalyzed reaction in human liver microsomes. But the mechanism of inhibition was slightly different between them Water extract of licorice mainly inhibited CYP2C19, and glycyrrhizin primarily inhibited CYP1A2. The inhibition by water extract of licorice and glycyrrhizin on CYP isoforms may cause drug interaction with co-administered drug leading to toxicity or treatment failure.

• Journal of Plant Biotechnology
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• v.30 no.1
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• pp.81-95
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• 2003

Carotenoids are synthesized from the plastidic glyceraldehyde-3-phosphate (GAP)/pyruvate pathway in isoprenoids biosynthetic system of plants. They play a crucial role in light harvesting, work as photoprotective agents in photosynthesis of nature, and are also responsible for the red, orange and yellow colors of fruits and flowers in plants. In addition to biological actions of carotenoids as antioxidants and natural pigments, they are essential components of human diet as a source of vitamin A. It has been also suggested that some kinds of carotenoids might provide protection against cancer and heart disease as human medicines. In this article, we review the commercial applications on the basis of biological functions of carotenoids, summarize the studies of genes involved in the carotenoid biosynthetic pathway, and introduce recent results achieved in metabolic engineering of carotenoids. This effort for understanding the carotenoids metabolism will make us to increase the total carotenoid contents of crop plants, direct the carotenoid biosynthetic machinery towards other useful carotenoids, and produce a new array of carotenoids by further metabolizing the new precursors that are created when one or two key enzymes in carotenoid biosynthetic pathway are exchanged through gene manipulation in the near future.

• Applied Microscopy
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• v.36 no.4
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• pp.291-297
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• 2006

To evaluate the effects of ingestion of alcoholic drinks on the toxicities of industrial compounds, cyclohexane (CH) was intraperitoneally administrated to rats (1.56g/kg body weight), which had been ingested 15% ethanol for up to 6 weeks,4 times by once a day and every other day. Following the last treatment of ethanol or CH, blood and liver tissues were collected after 4 hours prior to sacrifice of animals. By the injection of CH, liver weight (% of body weight) and xanthine oxidase activity in serum were increased, and glucose-6-phasphatase (G6P) activity in liver was decreased compared to them of control group. The activities of CH metabolizing enzymes, such as cytochrome P450 dependent aniline hydroxylase (CYPdAH) and alcohol dehydrogenase (ADH), were significantly increased by injection of CH, and those activities were the highest in CH-injected group after pretreated with alcohol. Ultrastructurally. both of alcohol treatment and CH injection induced transforming into the smooth-endoplasmic reticulum from rough-endoplasmic reticulum, the those rate was the highest in case of CH-injection after pretreated with alcohol. From these results, it is suggested that alcohol intake on a level without alcoholic degeneration of hepatocytes could enhance the CH metabolism of liver.