• Environmental Mutagens and Carcinogens
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• v.16 no.2
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• pp.97-102
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• 1996

In this study, we have quantified genotype frequency of the cytochrome P450 (P450) 2E1 which codes for the P450 enzyme primarily responsible for the metabolic activation of carcinogenic nitrosamines and low molecular organic solvents, in Korean population by using PCR and RFLP at two sites previously associated with some cancers; a PstI and RsaI RFLP in the transcriptional regulatory region of the human P450 2E1 gene. The genotype frequencies of homozygous wild type (PstI site-absent) and heterozygous mutant type (PstI site-present) in PstI RFLP were 0.70 and 030, respectively. The homozygous mutant type in Pstl RFLP was not observed in Korean population. The genotype frequencies of homozygous wild type (RsaI site-present), heterozygous mutant type (RsaI site-absent), and homozygous mutant type in RsaI RFLP were 0.71, 0.26, and 0.03, respectively.

• YAKHAK HOEJI
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• v.37 no.1
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• pp.95-99
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• 1993

Peroxidase activity of cytochrome P-450 was examined using N, N-dimethylaniline (NDA) as a substrate and cumene hydroperoxide (CHP) as an oxidant. The initial rates of the N-demethylation for varied concentrations of NDA (0.05-0.5 mM) by P-450 at different fixed concentrations of CHP (0.02-0.2 mM) were determined. The results suggest that P-450 proceeds its peroxidative reaction by the rapid equilibrium random bi bi mechanism to form a ternary complex with substrate and oxidant as an active intermediate.

• Archives of Pharmacal Research
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• v.27 no.2
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• pp.199-205
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• 2004

Cytochrome P450 (P450) 1 enzymes such as P450 1A1, 1A2, and 181 are known to be involved in the oxidative metabolism of various procarcinogens and are regarded as important target enzymes for cancer chemoprevention. Previously, several hydroxystilbene compounds were reported to inhibit P450 1 enzymes and were rated as candidate chemopreventive agents. In this study, we investigated the inhibitory effect of 2-[2-(3,5-dimethoxyphenyl)vinyl]-thiophene (DMPVT), produced from the chemical modification of oxyresveratrol, on the activities of P450 1 enzymes. The inhibitory potential by DMPVT on the P450 1 enzyme activity was evaluated with the Escherichia coli membranes of the recombinant human cytochrome P450 1A1, 1A2, or 1B1 coexpressed with human NADPH-P450 reductase. DMPVT significantly inhibited ethoxyresorufin O-deethylation (EROD) activities with $IC_{50}$ values of 61, 11, and 2 nM for 1A1, 1A2, and 1B1, respectively. The EROO activity in OMBA-treated rat lung microsomes was also significantly inhibited by OMPVT in a dose-dependent manner. The modes of inhibition by DMPVT were non-competitive for all three P450 enzymes. The inhibition of P450 1B1-mediated EROD activity by OMPVT did not show the irreversible mechanism-based effect. The loss of EROD activity in P450 1B1 with OMPVT incubation was not blocked by treatment with the trapping agents such as glutathione, N-acetylcysteine, or dithiothreitol. Taken together, the results suggested DMPVT to be a strong noncompetitive inhibitor of human P450 1 enzymes that should be considered as a good candidate for a cancer chemopreventive agent in humans.

• Journal of the Korean Society of Food Science and Nutrition
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• v.24 no.6
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• pp.859-866
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• 1995

This study was done to investigate the effects of chronic ethanol feeding on hepatic microsomal cytochrome system, lipid peroxidation and peroxide metabolizing enzyme activities in 2-acetylaminofluorene(2-AAF) treated rats. Male Sprague-Dawley rats, weighing 120~125g, were pair-fed liquid diets containing 35% of total calories either as ethanol or isocaloric carbohydrates for 6 weeks. After 4 weeks of experimental diet feeding, 2-AAF(100mg/kg body weight) was injected twice a week intraperitoneally. Both weight and percent liver weight per body weight were significantly changed by ethanol feeding. Hepatic microsomal lipid peroxide value and the activities of glutathione(GSH) peroxidase and GSH reductase were not changed by either ethanol or 2-AAF treatment. However the analysis of cytochrome systems showed that both ethanol and 2-AAF increased cytochrome P-450 and bs contents although cytochrome P-450 content was moe affected by 2-AAF while cytochrome b5 content by ethanol. Cytosolic GSH S-transferase activity, which is often elevated during chemical carcinogenesis, also significantly increased by either ethanol feeding or 2-AAF treatment. Overall values for the cytochrome contents and GSH S-transferase activities were highest in 2-AAF treated rats fed ethanol. These results might support the hypothesis that the increase in liver cancer risk associated with chronic ethanol consumption might be due to, at least in part, enhancement of carcinogen bioactivation by ethanol.

• Journal of Food Hygiene and Safety
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• v.11 no.4
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• pp.291-297
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• 1996

The role of cytochrome P-450 2E1 (P450 2E1) in the early phase of alcoholic fatty liver was examined. Female rats were pretreated with either allyl sulfide (200 mg/kg, po), disulfiram (500 mg/kg, po), YH 439 (250 mg/kg, po) or pyrazine (200 mg/kg/day$\times$2 days, ip). Marked changes in carbon tetrachloride-induced hepatotoxicity and caboxyhemoglobin (COHb) elevation due to dichloromethane administration were observed in rats treated with one of the P450 2E1 modulators. A single dose of ethanol (6 g/kg, po) increased the hepatic triglyceride contents approximately 2 fold, which was inhibited completely by YH 439 pretreatment. However, the other P450 2E1 modulators failed to alter the ethanol-induced hepatic triglyceride accumulation. In vitro hepatic microsomal enzyme activity was determined in 4 week old premature and 12 week old adult rats. Aminopyrine-N demethylation was not different, but p-nitrophenol hydroxylation and p-nitroanisole O-demethylation were significantly higher in premature rats. However, no difference in the triglyceride accumulation induced by an intraperitoneal dose of ethanol (3 g/kg) was noted between premature and adult rats. The results suggest that the P450 2E1 activity dose not play an important role in the induction of acute alcoholic fatty liver.

• 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

• Journal of Society of Preventive Korean Medicine
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• v.15 no.1
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• pp.1-16
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• 2011

Objectives : The mechanisms for korean traditional medicine-drug interaction has not been well reviewed in spite that the chance for co-administration with western drugs or diet supplements has been increased. Especially, it is well known that various cytochrome P450s play a major role in drug-drug interaction. Of course, Korean traditional medicines is not excluded in a view of metabolism or biotransformation by cytochrome P450. This article was focused on reviewing the possible roles of cytochrome P450 in Korean traditional medicine-drug interaction, Also, the directions for further studies were suggested in terms of Korean traditional medicine-drug interaction. Methods : New studies for korean traditional medicine-drug interaction were reviewed and summarized in terms of cytochrome P450 activities by various Korean traditional medicines and western drugs. Results and Conclusions : Even if a few studies related to Korean traditional medicine-drug interactions was carried out, almost no studies for Korean traditional medicine-drug interactions has been found in a view of cytochrome P450. It was suggested that Korean traditional medicines and their decoction should be analyzed that how they effects on cytochrome P450, expecially CYP 1, 2, 3 families and how they interact with western drugs.

• Journal of Microbiology and Biotechnology
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• v.15 no.1
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• pp.183-187
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• 2005

Abstract The cancer chemopreventive potential of chitosanoligosaccharides was investigated by measuring the induction of quinone reductase and glutathione S-transferase activities and inhibition of cytochrome P450 1A1, 2B1, and 2E1 activities. Chitosanoligosaccharide I (1-${\kappa}$Da${\kappa}$Da) significantly induced glutathione S-transferase activity with a maximal 1.5-fold increase at 500 ${\mu}$g/ml, while chitosanoligosaccharide II (3-${\kappa}$Da${\kappa}$Da) (500 ${\mu}$g/ml) strongly induced quinone reductase (p<0.01) and glutathione S-transferase (p<0.005) activities. The in vitro incubation of rat liver microsomes with chitosanoligosaccharides I and II (2.5, 5, 50, and 500 ${\mu}$g/ml) showed a dose-dependent inhibiton of cytochrome P450 1A1, 2B1, and 2E1 activities. Chitosanoligosaccharide II was a more potent inhibitor of cytochrome P450 2B1 activity than chitosanoligosaccharide I. Accordingly, these findings suggest that chitosanoligosaccharides are potential chemopreventive agents.

• Biomedical Science Letters
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• v.1 no.1
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• pp.89-94
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• 1995

Considering the planar structure and nonpolar properity of benzo(a)pyrene(B(a)p) and the planar heme part of cytochrome P-450, stacking interaction is probable. MO calculation on B(a)P and heme part of cytochrome P-450 were carried out to dertermine probable stacking interaction models. In this case, orbital interaction is most important. Accordingly, the stacking positions have high eigen vector in frontier orbital and boning type between two molecules. In this way, five probate models were selected and examined by MN2 and MO method. The most probable .stacking interaction model which is the 4, 5, 6 positions of B(a)P overlap carbon atom and pyrrole ring of ring of heme group was determined.

• Korean Journal of Acupuncture
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• v.21 no.2
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• pp.139-145
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• 2004

Objectives : Inhibition of phase I enzymes such as cytochrome P450 (CYP) 1A1 or 1A2 is considered a major mechanism of protection against initiation of carcinogenesis. The inhibition of toxic enzymes and CYP were studied with so many oriental herbral medicine. Recently, numerous polysaccharides and polysaccharide-protein complexes have been isolated from mushrooms and used as a source of therapeutic agents. The most promising biopharmacological activities of these polymers are their immunomodulation and anti cancer. But, in this study the inhibitory effect was on the aqua-acupuncture of Lentinus edodes. Materials : Lentinus edodes aqua-acupuncture solution (LEAS) was prepared and tested for the inhibition of cytochrome P450 (CYP) 1A1 and 1A2 activities. LEAS type I from fruit body of these mushrooms. Type II was extracted from cultured broth of Lentinus edodes mycelum. Results : LEAS type I and type II were significantly inhibited CYP 1A1 and 1A2 enzymes at concentration of 5.0 and 10.0 mg/ml. Conclusion : These results suggested that LEAS may act as block agent against carcinogenesis by inhibition of phase I enzymes.