• Proceedings of the PSK Conference
• /
• 2003.10b
• /
• pp.112.2-112.2
• /
• 2003

CYP1 enzymes, CYP1A1, CYP1A2 and CYP1B1, are known to bioactivate procarcinogens particularly polyaromatic compounds. Flavonoids are a class of natural compounds that are present in edible plants. Structurally, these compounds are polyphenols with two aromatic rings (A, B) and a heterocycyclic ring (C). We observed the differential inhibition of 5,7-dihydroxyflavones which are different in numbers of B-ring-OH, to the activity of ethoxyresorufin O-deethylase (EROD) in human hepatic microsomes with the IC50 values, ie, 0.57 mM, 1.28 mM, and 3.62 mM, chrysin, apigenin, and Luteolin, respectively. (omitted)

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.9
• /
• pp.4071-4077
• /
• 2014

Background: The effects of CYP1A1 gene polymorphisms on the risk of bladder cancer (BC) remain controversial. We carried out a meta-analysis to clarify the role of CYP1A1 gene polymorphisms in BC. Material and Methods: A comprehensive literature search was conducted up to November 20, 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of the association. Meta-regression, subgroup analysis, sensitivity analysis and publication bias were also performed. Results: Eight studies involving 1,059 BC cases and 1,061 controls were included. The meta-analysis showed that there was no significant association between the two common mutations of CYP1A1 and BC risk. For the I1e462Val A/G polymorphism with GG vs. AA the OR was 1.47 (95 % CI= 0.70-3.07, P =0.308). For the MspI T/C polymorphism, though a slight trend was found this was not statistically nonsignificant (CC vs.TT, OR = 1.24, 95 % CI= 0.98-1.58, P =0.078). Subgroup analyses by ethnicity also found no obvious association between CYP1A1 and BC risk. Conclusion: The present meta-analysis suggests that CYP1A1 polymorphism is not associated with bladder cancer risk.

• Journal of Marine Life Science
• /
• v.7 no.2
• /
• pp.145-153
• /
• 2022

Mercury (Hg) is a major concern in marine environment because of their bioaccumulation and biomagnification properties, and adverse effects to aquatic organisms at even a trace amount. However, little information on the effects of Hg, compared to other heavy metals, is available in marine small crustaceans. Here, we investigated the transcriptional modulation of metabolism-related genes in the brackish water flea, Diaphanosoma celebensis after exposure to sublethal concentration (0.2, 0.4, 0.8 ㎍/l) of HgCl₂ for 48 h. Relative mRNA expression levels of five detoxification enzyme-coding genes (cytochrome P450; cyp360A1, cyp361A1, cyp4AP3, cyp4C122, and cyp370C5) and six digestive enzyme-coding genes [alpha amylase (AMY), alpha amylase related protein (AMY-like), trypsin (TRYP), chymotrypsin-like protein (CHY), lipase (LIP), pancreatic lipase-related protein (PLRP)] were analyzed using quantitative real time reverse transcription polymerase chain reaction (qRT-PCR). As results, Hg increased the mRNA level of cyp370C5 (clan2) and cyp4AP3 (clan4) in a concentration dependent manner. A significant increase in TRYP mRNA was also concentration-dependently observed after exposure to Hg. These findings suggest that cyp370C5 and cyp4AP3 play a key role in Hg detoxification in D. celebensis, and Hg can affect energy metabolism by modulating the transcription of digestive enzyme. This study will provide better understanding the molecular effects of Hg in marine small crustacean.

• Journal of Pharmaceutical Investigation
• /
• v.37 no.6
• /
• pp.369-376
• /
• 2007

Cyclosporine (CsA) and tacrolimus (FK506) have a narrow therapeutic range, and their pharmacokinetic (PK) characteristic varies among individual. They are also substrates for cytochrome P450 (CYP) 3A4, 3A5 genes, and P-glycoprotein, the product of the multidrug resistance 1 (MDR1). The aims were to investigate the relationship between CYP3A and MDR1 genotypes and their PK parameters among healthy subjects. We investigated the genotype for CYP3A and MDR1 gene in human using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. After oral administration of CsA and FK506 (100 mg and 1 mg, respectively), whole blood samples were taken up to 24 hours. Blood CsA and FK506 concentrations were measured by LC/MS/MS. Each PK parameters were compared using Kruskal-Wallis test according to the CYP3A and MDR1 genotype. We found that the values of AVC for CsA were significantly different among CYP3A5 and MDR1 exon 26 (C3435T) genotypes (P=0.037 and P=0.049). On the other hand, the AUC for FK506 was significantly different only among CYP3A5 genotypes (P=0.013). The results clearly demonstrate the effects of CYP3A5 and MDR1 exon 26 on Cys and FK506 disposition.

• Environmental Mutagens and Carcinogens
• /
• v.23 no.1
• /
• pp.23-29
• /
• 2003

To determine the frequencies of the genotypes of estrogen metabolising enzyme (CYP17, CYP1A1, CYP1B1, and COMT) and to identify the high-risk genotypes of these metabolic enzymes to breast cancer in Korean, the author has analysed 115 breast cancer patients and corresponding age and sex matched heathy controls using polymerase chain reaction-restiction fragment length polymorphism (PCR-RFLP). A2/A2 genotype in CYP17 polymorphism, m2/m2 genotype in CYP1A1 polymorphism, and Val/Val genotype in CYP1B1 had 0.95, 1.40 and 0.76 relive risks to breast cancer comparing with reference genotypes of each polymorphism, respectively. Among the genotypes of COMT enzyme polymorphism, L/H and L/L genotypes had 0.97 and 1.54 relative risks to breast cancer, respectively. According to the number of high risk genotype, the patients with one or two putative high risk genotypes had 0.95 and 1.94 relative risks to breast cancer, respectively. This study have demonstrated the unique frequency of genotypes of estrogen metabolizing enzyme in Korean healthy women, which will provide the basic data and insights to study the estrogen related conditions in Korean women including breast and endometrial cancers. And it also indicates that the well-known high risk genotypes of estrogen metabolizing enzymes are not significantly associated with the development of breast cancer in Korean women.

• Archives of Pharmacal Research
• /
• v.27 no.8
• /
• pp.857-862
• /
• 2004

Naringenin, dietary flavonoid, is antioxidant constituents of many citrus fruits. In the present study, we investigated the effect of naringenin on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible CYP1 A 1 gene expression in mouse hepatoma Hepa-1c1c7 cells. Naringenin alone did not affect CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity. In contrast, the TCDD-inducible EROD activities were markedly reduced upon concomitant treatment with TCDD and naringenin in a dose dependent manner. TCDD-induced CYP1A1 mRNA level was also markedly suppressed by naringenin. A transient transfection assay using dioxin-response element (DRE)-linked luciferase and electrophoretic mobility shift assay revealed that naringe-nin reduced transformation of the aryl hydrocarbons receptor(AhR) to a form capable of specif-ically binding to the DRE sequence in the promoter of the CYP1A1 gene. These results suggest the down regulation of the CYP1A1 gene expression by either naringenin in Hepa-1c1c7 cells might be antagonism of the DRE binding potential of nuclear AhR.

• Journal of Korean Society of Occupational and Environmental Hygiene
• /
• v.19 no.1
• /
• pp.73-79
• /
• 2009

This study was undertaken to investigate the effects of single and combined exposure of toluene (T) and xylene (X) on the cytochrome-450(CYP)-mediated metabolizing capacity, induction of CYP isozymes and the excretion of their metabolites in urine. Animal were adults male Sprague-Dawley (SD) rats and divided into 4 groups such as control, T (treated with 63.7 mg/body kg), X (treated with 65.9 mg/body kg) and TX(T=X). Organic solvents was administrated by intraperitoneal injection for 3 days. The contents of protein and CYP in liver microsomes of control group were $16.48{\pm}0.56 mg/m{\ell}$ and $0.744{\pm}0.025$ nmol/mg protein, respectively, and they contents were significantly lower than in derived from treated groups (p<0.01). The activities of PROD and ${\rho}NPH$ were significantly higher in single treated groups than in control and combined group (TX). When Western immunoblotting were carried out with two monoclonal antibodies (MAb 1-98-1 and MAb 2-66-3) which were specific against CYP2B1/2 and CYP2E1, respectively, a strong signal corresponding to CYP2B1/2 was observed in microsomes obtained from rats treated with X and TX. The color density against CYP2E1 was slightly increased in T and TX groups compared with C and X groups. The amounts of urinary hippuric acid in T single treated group was $3.29{\pm}1.97$ g/g creatinine and TX combined group was $2.91{\pm}1.76$ g/g creatinine, but was not significant. However, amount of urinary methy hippuric acid in X single treated group ($1.62{\pm}0.72$ g/g creatinine) was significantly higher than TX combined group ($0.93{\pm} 0.63$ g/g creatinine)(p<0.01). These results suggested that CYP2E1 isozyme might be responsible for the metabolism of T, and CYP2B1/2 isozyme is for X. And also, difference of metabolites level between single and combined group may be speculated that the intermediates of T and X interacted each other in the process of their metabolite formation reaction.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.13
• /
• pp.5207-5214
• /
• 2014

Background: To study the relationship of susceptibility to lung cancer with the gene polymorphisms of CYP1A1, GSTM1, GSTM3, GSTT1, GSTP1 and smoking status in Han and Mongolian populations of Inner Mongolia, an autonomous region of China. Materials and Methods: PCR-RFLP, allele-specific and multiplex PCR were employed to identify the genotypes of CYP1A1, GSTM1, GSTM3, GSTT1 and GSTP1 in a case-control study of 322 lung cancer patients diagnosed by bronchoscopy and 456 controls free of malignancy. Results: There is a significant difference in genotypic frequency of GSTT1 of healthy Mongolian and Han subjects. A statistically prominent association was found between CYP1A1 Msp1 (vt/vt) (OR=4.055, 95%CI:2.107-7.578, p=0.000), GSTM1 (-) (OR=2.290, 95%CI:1.467-3.573, p=0.000) and lung cancer in Mongolians. Similarly, in the Han population, CYP1A1 Msp1 (vt/vt) (OR=3.194, 95%CI:1.893-5.390, p=0.000) and GSTM1 (-) (OR=1.884, 95%CI:1.284-2.762, p=0.001) carriers also had an elevated risk of lung cancer. The smokers were more susceptible to lung cancer 2.144 fold and 1.631 fold than non-smokers in Mongolian and Han populations, respectively. The smokers who carried with CYP1A1 Msp1 (wt/vt+vt/vt), exon7 (Val/Val+Ile /Val), GSTM1 (-), GSTM3 (AB+BB), and GSTT1 (-) respectively were found all to have a high risk of lung cancer. Conclusions: CYP1A1 Msp1 (vt/vt) and GSTM1 (-) are risk factors of lung cancer in Han and Mongolian population in the Inner Mongolia region. The smokers with CYP1A1 Msp1 (wt/vt+vt/vt), CYP1A1 exon7 (Val/Val+Ile /Val), GSTM1 (-), GSTM3 (AB+BB), and GSTT1 (-) genotypes, respectively, are at elevated risk of lung cancer.

• International Journal of Oral Biology
• /
• v.31 no.3
• /
• pp.107-112
• /
• 2006

Aldehyde dehydrogenase (ALDH) plays an important role in alcohol metabolism; ALDH is responsible for the oxidation of acetaldehyde generated during alcohol oxidation. ALDH is also known to oxidize various other endogenous and exogenous aldehydes. Cytochrome P-450 2E1 (CYP2E1), a liver microsomal enzyme, also metabolizes acetaldehyde and ethanol and can be induced by other inducers including acetone and ethanol. We examined single nucleotide polymorphisms (SNP) of ALDH and CYP2E1 genotypes in Korean. Restriction fragment length polymorphism (RFLP) method was used to determine ALDH and CYP2E1 SNP. Mutation in ALDH was 60% (heterozygote 46.7% and homozygote 13.3%) among 15 cases. CYP2E1 mutation was 52.7% (heterozygote 47.4% and homozygote 5.3%) among 19 cases.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.1
• /
• pp.57-64
• /
• 2016

Background: Tobacco smoking is considered a risk factor for cervical cancer development due to the presence of tobacco based carcinogenic metabolites in cervical cells of female smokers. In this study, we investigated the role of the T3801C (MspI) polymorphism of CYP1A1, a gene encoding an enzyme necessary for the initiation of tobacco based carcinogen metabolism, on cervical cancer risk. The T to C substitution may alter CYP1A1 activities, potentially elevating cervical cancer risk. Since results of gene-disease association studies vary according to the study population, the multi-ethnic population of Malaysia provides an excellent representative cohort for identifying and comparing the cervical cancer risk among the 3 major ethnics in Southeast Asia in relation to CYP1A1 MspI polymorphism. Materials and Methods: A total of 195 Thin Prep Pap smear samples from HPV negative and cancer free females were randomly selected as controls while 106 formalin fixed paraffin embedded samples from females with invasive cervical cancer were randomly selected for the cases group. The polymorphisms were identified using restriction fragment length polymorphism (RFLP) PCR. Results: We found no significant associations between CYP1A1 MspI polymorphism and cervical cancer in the general Malaysian female population. However, upon ethnic stratification, the variant C/C genotype was significantly associated with a 4.66-fold increase in cervical cancer risk in Malay females (95% CI= 1.21-17.9; p=0.03). No significant association was observed in the Chinese and Indian females. Additionally, there were no significant associations in the dominant model and allele frequency model analysis in both the general and ethnically stratified female population of Malaysia. Conclusions: Our findings suggest that the C/C genotype of CYP1A1 MspI polymorphism is associated with the development of cervical carcinoma in the Malay females of Malaysia.