• Toxicological Research
• /
• v.32 no.2
• /
• pp.89-93
• /
• 2016

Human cytochrome P450 enzymes (P450s, CYPs) are major oxidative catalysts that metabolize various xenobiotic and endogenous compounds. Many carcinogens induce cancer only after metabolic activation and P450 enzymes play an important role in this phenomenon. P450 1B1 mediates bioactivation of many procarcinogenic chemicals and carcinogenic estrogen. It catalyzes the oxidation reaction of polycyclic aromatic carbons, heterocyclic and aromatic amines, and the 4-hydroxylation reaction of $17{\beta}$-estradiol. Enhanced expression of P450 1B1 promotes cancer cell proliferation and metastasis. There are at least 25 polymorphic variants of P450 1B1 and some of these have been reported to be associated with eye diseases. In addition, P450 1B1 polymorphisms can greatly affect the metabolic activation of many procarcinogenic compounds. It is necessary to understand the relationship between metabolic activation of such substances and P450 1B1 polymorphisms in order to develop rational strategies for the prevention of its toxic effect on human health.

• Journal of Nutrition and Health
• /
• v.23 no.1
• /
• pp.11-18
• /
• 1990

Sprague-Dawley male rats were fed the diet of p/s 4.0(soybean oil : I), p/s 0.08(Beef tallow : II) at the level of 15% fat until 8 weeks after weaning. I & II groups were divided into 4 sub-groups by diets with or without 0.3% butylated hydroxytoluene(BHT). 2-AAF was injected at the age of $5_{1/2}$, 6, $5_{1/2}$, 7 weeks. MFO system enzyme(cytochrome p-450, cytochrome p-450 reductase, cytochrome b5) activities and lipid peroxide were determined from isolated liver microsome. 2-AAF injected young rats had growth retardatiion. Lipid peroxide values were not influenced greatly by dietary fat, 2-AAF and BHT. Cytochrome p-450 contents were increased in I-BHT-AAF & II-AAF groups by 2-AAF and its contents were not affected by BHT. But cytochrome p-450 and cytochrome p-450 reductase were not increased in soybean oil diet ybean oil groups. Cytochrome b5 was not influenced by dietary fat, 2-AAF and BHT. Cytochrome p-450 and lipid peroxide, cytochrome p-450 reductase and cytochrome b5, which transfer to MFO system, appeared to have positive correlations(r=0.2474, r=0.2475, p<0.05) each other. This result suggests that MFO system metabolizing 2-AAF was influenced by dietary fats and BHT. 2-AAF induced growth retardation in young rats.

• Toxicological Research
• /
• v.13 no.4
• /
• pp.385-391
• /
• 1997

Inductive effects of cytochrome P450 2B1 by $\alpha$- and $\beta$-ionone were characterized in individual liver lobes of male Sprague Dawley rats. When rats were administered ionones orally at 100, 300, and 600 mg/kg for 24 hr, cytochrome P450 2B1 was induced dose-dependently in liver S-9 fractions as measured by P450 2B-specific monooxygenases and Western immunoblotting. The activity of P450 1A- and P450 2B-specific monooxygenases was differentially expressed in each lobe of normal liver. In addition, the monooxygenase activity was induced by $\alpha$- and $\beta$-ionone with different potency in each lobe of the liver. Our present results indicate that the different induction of P450s by $\alpha$- and $\beta$-ionone in each lobe may explain different susceptibilities of rat liver lobes to certain hepatotoxicants which require metabolic activation for their toxicity and that $\alpha$- and $\beta$-ionone may be useful model inducers of P450 2B1 in studying the toxic mechanism of certain toxicants which may require the metabolic activation by P450.

• Proceedings of the PSK Conference
• /
• 2003.10b
• /
• pp.148.2-149
• /
• 2003

Recently we have reported that various hydroxystilbenes show strong inhibition of human cytochrome P450 1 enzyme activities. A series of syntheic trans-stilbene derivatives were prepared and their inhibitory potentials were evaluated with the bacterial membrane of recombinant human cytochrome P450 1A1, 1A2 and 1B1 coexpressed with hyman NADPH-P450 reductase to find a new inhibitor of cytochrome P450 enzymes. Of the compounds tested, SY-081 exhibited a potent inhibition of human cytochrome P450 1B1 with an $IC_50$ value of 2.6 nM. (omitted)

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

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

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

• Applied Biological Chemistry
• /
• v.38 no.2
• /
• pp.168-173
• /
• 1995

To investigate the effects of endosulfan on cytochrome P-450 enzymes in mouse(Balb c.), endosulfan was given by an intraperitoneal dose of 7.5 mg/kg. The treatment of endosulfan increased the cytochrome P-450 content by 3.3 to 4.2 fold, cytochrome $b_5$ content by 2.3 to 3.8 fold, NADPH cytochrome P-450 reductase activity by 5.3 to 6.4 fold and total haem content by 3.1 to 3.6 fold of mouse liver after 48 hrs of intraperitoneal injection. Endosulfan cytochrome P-450 absorption spectrum exhibited miximum at 387 nm and 389 nm and broad near 407 nm in the liver microsome. Reduced P-450-CO spectrum of the liver microsome exposed by the treatment of endosulfan showed maximum at 449 nm and 450 nm compared to that of the control having maximum at 451 nm, which indicated endosulfan induced cytochrome P-450 new isozymes. Aldrin epoxidase activities in the mouse liver and kidney were increased by 2.8 and 2.1 fold by the treatment of endosulfan. Also 7-ethoxyresorufin dealkylase activities in the mouse liver and kidney were elevated by 1.7 and 1.8 fold by treatment of endosulfan.

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

• The Korean Journal of Mycology
• /
• v.31 no.1
• /
• pp.34-39
• /
• 2003

This study was conducted to investigate effects of Ramaria botrytis methanol extract on liver damage in benzo$({\alpha})$pyrene(B$({\alpha})$P)-treated mice. The activities of serum amminotransferase, cytochrome P-450, aminopyrine N-demethylase, aniline hydroxylase and hepatic content of lipid peroxide after B$({\alpha})$P-treatment were increased than control, but those levels were significantly decreased by the treatment of Ramaria botrytis methanol extract. Whereas, the hepatic glutathione content and activities of glutathionie S-transferase and r-glutamylcysteine syntherase were increased by the treatment of Ramaria botrytis methanol extract. In addition, cytochrome P-450 1A1 izozyme protein level, remarkably increased by B$({\alpha})$P-treatment was decreased by the treatment with methanol extract of Ramaria botrytis. These results suggest that the protective effect of methanol extract of Ramaria botrytis on liver injury in B$({\alpha})$P-treated mice may be due to reduction of oxygen free radical.