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

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.82-88
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• 2023

Genomic analysis indicated that the genome of Drosophila melanogaster contains more than 80 cytochrome P450 genes. To date, the enzymatic activity of these P450s has not been extensively studied. Here, the biochemical properties of CYP6A8 were characterized. CYP6A8 was cloned into the pCW vector, and its recombinant enzyme was expressed in Escherichia coli and purified using Ni²⁺-nitrilotriacetate affinity chromatography. Its expression level was approximately 130 nmol per liter of culture. Purified CYP6A8 exhibited a low-spin state in the absolute spectra of the ferric forms. Binding titration analysis indicated that lauric acid and capric acid produced type I spectral changes, with K_d values 28 ± 4 and 144 ± 20 µM, respectively. Ultra-performance liquid chromatography-mass spectrometry analysis showed that the oxidation reaction of lauric acid produced (ω-1)-hydroxylated lauric acid as a major product and ω-hydroxy-lauric acid as a minor product. Steady-state kinetic analysis of lauric acid hydroxylation yielded a k_cat value of 0.038 ± 0.002 min^-1 and a K_m value of 10 ± 2 µM. In addition, capric acid hydroxylation of CYP6A8 yielded kinetic parameters with a k_cat value of 0.135 ± 0.007 min^-1 and a K_m value of 21 ± 4 µM. Because of the importance of various lipids as carbon sources, the metabolic analysis of fatty acids using CYP6A8 in this study can provide an understanding of the biochemical roles of P450 enzymes in many insects, including Drosophila melanogaster.

• Korean Journal of Environmental Biology
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• v.21 no.2
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• pp.170-176
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• 2003

The effect of xenobiotics on cytochrome P450 (CYP) and 7-ethoxyresorufin-O-deethylase (EROD) in hepatopancreatic microsome of surf clam, Coelomactra anti-quata, were investigated. The microsome isolated from the digestive gland of the surf clam, collected from the east coast of Korea, was in vitro exposed to p, p -DDT (0.1,0.4 and 1.0 mM) for 30 min and 2,3,7,8-TCDD (0.01, 0.04 and 0.1 ppb) and PCB-153 (0.01, 0.04 and 0.1 ppb) for 7 hr. In the case of DDT exposure, the CYP content and EROD activity of 1.0 mM exposure group increased up to about 117% and 120% of the DMSO solvent control group after 10 min. exposure, respectively. After 2 hr exposure of TCDD, the CYP content and EROD activity were also induced to the range of 103∼110% and 121∼139%, respectively. The PCB-153 exposure group showed 107∼115% of CYP content and 129∼140% of EROD activity after 2 hr exposure. Three test chemicals apparently induced CYP and EROD activity in the microsome of surf clam. The inducing potentials depend en the test chemicals.

• Journal of Ginseng Research
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• v.35 no.3
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• pp.272-282
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• 2011

Ginseng (Panax ginseng Meyer) has been shown to have anti-aging effects in animal and clinical studies. However, the molecular mechanisms by which ginseng exerts these effects remain unknown. Here, the anti-aging effect of Korean red ginseng (KRG) in rat testes was examined by system biology analysis. KRG water extract prepared in feed pellets was administered orally into 12 month old rats for 4 months, and gene expression in testes was determined by microarray analysis. Microarray analysis identified 33 genes that significantly changed. Compared to the 2 month old young rats, 13 genes (Rps9, Cyp11a1, RT1-A2, LOC365778, Sv2b, RGD1565959, RGD1304748, etc.) were up-regulated and 20 genes (RT1-Db1, Cldn5, Svs5, Degs1, Vdac3, Hbb, LOC684355, Svs5, Tmem97, Orai1, Insl3, LOC497959, etc.) were down-regulated by KRG in the older rats. Ingenuity Pathway Analysis of untreated aged rats versus aged rats treated with KRG showed that the affected most was Cyp11a1, responsible for C21-steroid hormone metabolism, and the top molecular and cellular functions are organ morphology and reproductive system development and function. When genes in young rat were compared with those in the aged rat, sperm capacitation related genes were down-regulated in the old rat. However, when genes in the old rat were compared with those in the old rat treated with KRG, KRG treatment up-regulated C21-steroid hormone metabolism. Taken together, Cyp11a1 expression is decreased in the aged rat, however, it is up-regulated by KRG suggesting that KRG seems enhance testes function via Cyp11a1.

• Journal of Preventive Medicine and Public Health
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• v.55 no.3
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• pp.280-288
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• 2022

Objectives: One of the most widely used pesticides today is chlorpyrifos (CPF). Cytochrome P450 (CYP)2B6, the most prominent catalyst in CPF bioactivation, is highly polymorphic. The objective of our study was to evaluate the role of CYP2B6^*6, which contains both 516G>T and 785A>G polymorphisms, in CPF toxicity, as represented by the concentration of 3,5,6-trichloro-2-pyridinol (TCPy), among vegetable farmers in Central Java, Indonesia, where CPF has been commonly used. Methods: A cross-sectional study was conducted among 132 vegetable farmers. Individual socio-demographic and occupational characteristics, as determinants of TCPy levels, were obtained using a structured interviewer-administered questionnaire and subsequently used to estimate the cumulative exposure level (CEL). TCPy levels were detected with liquid chromatography-mass spectrometry. CYP2B6^*6 gene polymorphisms were analyzed using a TaqMan^® SNP Genotyping Assay and Sanger sequencing. Linear regression analysis was performed to analyze the association between TCPy, as a biomarker of CPF exposure, and its determinants. Results: The prevalence of CYP2B6^*6 polymorphisms was 31% for ^*1/^*1, 51% for ^*1/^*6, and 18% for ^*6/^*6. TCPy concentrations were higher among participants with CYP2B6^*1/^*1 than among those with ^*1/^*6 or ^*6/^*6 genotypes. CYP2B6^*6 gene polymorphisms, smoking, CEL, body mass index, and spraying time were retained in the final linear regression model as determinants of TCPy. Conclusions: The results suggest that CYP2B6^*6 gene polymorphisms may play an important role in influencing susceptibility to CPF exposure. CYP2B6^*6 gene polymorphisms together with CEL, smoking habits, body mass index, and spraying time were the determinants of urinary TCPy concentrations, as a biomarker of CPF toxicity.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.238.2-239
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• 2003

The purposes of this study were to evaluate the relationship between the genetic polymorphisms in CYP2D6*10 allele, MDR1 (exon 21 and 26) gene and risperidone pharmacokinetics in healthy male Korean subjects. A single dose of 2 mg risperidone tablet was given orally to 23 healthy male Korean volunteers. Blood samples were taken during the 12 hours after the dose. Serum concentrations of risperidone and 9-hydroxyrisperidone were measured using HPLC with UV detector. 23 subjects were genotyped for CYP2D6*10 allele, MDR1 G2677 T and C3435T by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). (omitted)

• Korean Journal of Biological Psychiatry
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• v.6 no.2
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• pp.189-192
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• 1999

The genetically determined CYP2D6 activity may be considered to be associated with antipsychotic induced extrapyramidal side effects with interindividual variation. Genetic polymorphism of CYP2D6 was determined by polymerase chain reaction(PCR) and MspI restriction fragment length polymorphisms(RFLP) for 194 schizophrenics. Subjects with a 334bp band were classified a1a1, those with 229bp and 105bp bands a2a2, and those with all three bands a1-a2. We did not identify schizophrenic subject with poor metabolizer. 194 schizophrenic patients previously treated neuroleptic medication, were assessed by Extrapyramidal Symptom Rating Scale(ESRS).The cases were composed of 33 akathisia, 47 parkinsonism, 21 tardive dyskinesia. These results are similar to the previous understanding that the poor metabolizer is very rare in Orientals compared to Caucasians, therefore, it considered that CYP2D6 genotypes have maybe no association with schizophrenia and extrapyramidal side effects in Koreans.

• Korean Journal of Clinical Pharmacy
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• v.21 no.2
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• pp.115-121
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• 2011

에토포시드와 아피제닌의 약동학적 상호작용 연구를 위하여 아피제닌 (0.4, 2.0 또는 8 mg/kg)과 에토포시드의 경구(6 mg/kg) 및 정맥 (2 mg/kg) 투여 하여 본 연구를 실시하였다. 아피제닌이 cytochrome P450 (CYP) 3A4 활성과 P-glycoprotein (P-gp)의 활성에 미치는 영향도 평가하였다. 아피제닌의 CYP3A4의 50% 효소활성억제는 $1.8{\mu}M$ 이었다. 아피제닌은 MCF-7/ADR 세포의 로다마인-123 세포 축적을 증가 시키므로 P-gp를 억제시켰다. 아피제닌은 에토포시드의 혈장곡선하면적과 최고혈장농도 (AUC and $C_{max}$)를 유의성 있게 증가시켰으나, 에토포시드의 최고혈장농도 도달시간 ($T_{max}$)과 생물학적 반감기 ($t_{1/2}$)에는 영향을 미치지 않았다. 따라서, 아피제닌 존재하에 에토포시드의 절대적생체이용률 (AB)은 대조군과 비교하여 유의성있게 증가되었다. 경구투여시와는 대조적으로, 아피제닌은 정맥 내로 투여된 에토포시드에서는 약동학적 파라미터에 어떤 영향도 미치지 않았다. 따라서 아피제닌이 에토포시드의 생체이용률을 증가시킨 것은 아피제닌이 소장과 간장에서 CYP3A4을 억제 및 소장에서 P-gp를 억제 시켰기 때문으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3253-3256
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• 2015

Background: Chronic hepatitis B virus (HBV) infection related hepatocellular carcinoma (HCC) is a major health problem in the Asia-Pacific region including Thailand. Several factors have been proposed as contributing to hepatocarcinogenesis. This study was aimed to investigate the impact of CYP2C19 genotypic polymorphism in HCC related to chronic HBV infection in Thailand. Materials and Methods: A cross-sectional study was performed between April 2014 and January 2015. Chronic HBV patients with HCC (n=50) and without HCC (n=50) were included. Clinical information and blood samples of all patients were collected. The CYP2C19 genotype was determined by polymerase chain reaction-restriction fragment length polymorphism method, and was classified as rapid metabolizer (RM), intermediate metabolizer (IM) or poor metabolizer (PM). Results: The CYP2C19 genotype frequencies of RM, IM and PM in HBV patients were found to be 19/50 (38%), 25/50 (50%) and 6/50 (12%), respectively. The CYP2C19 genotype frequencies of RM, IM and PM in HBV with HCC patients were 21/50 (42%), 25/50 (50%) and 4/50 (8%), respectively. The distribution of CYP2C19 genotype was not different between patients with and without HCC. Interestingly, among HBV with HCC patients, the RM genotype of CYP2C19 tended to increase risk of aggressive manifestation (OR=2.89, 95%CI=0.76-11.25, P-value=0.07), compared with non RM genotype carriers. Conclusions: CYP2C19 genotype IM was the most common genotype in Thai patients with chronic HBV infection. In addition, genotype RM could be an associated factor for aggressive presentation in HCC related to chronic HBV infection.

• Toxicological Research
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• v.23 no.2
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• pp.135-142
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• 2007

Formononetin is an isoflavonoid phytoestrogen found in certain foodstuffs such as soy and red clover. In this study, we examined the action of formononetin with the carcinogen activation pathway mediated through the aryl hydrocarbon receptor (AhR) in MCF-7 breast carcinoma cells. Treating the cells with formononetin alone caused the accumulation of CYP1A1 mRNA as well as elevation in CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity in a dose dependent manner. However, a concomitant treatment with 7,12-dimethylbenz[a]anthracene (DMBA) and formononetin markedly reduced both the DMBA-inducible EROD activity and CYP1A1 mRNA level. Under the same conditions, formononetin inhibited the DMBA-induced AhR transactivation, as shown by reporter gene analysis using a xenobiotic responsive element (XRE). Additionally, formononetin inhibited both DMBA-inducible nuclear localization of the aryl hydrocarbon receptor (AhR) and metabolic activation of DMBA, as measured by the formation of the DMBA-DNA adducts. Furthermore, formononetin competed with the prototypical AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), for binding to the AhR in an isolated rat cytosol. These results suggest that formononetin might be considered as a natural ligand to bind on AhR and consequently produces a potent protective effect against DMBA-induced genotoxicity. Therefore, that's the potential to act as a chemopreventive agent that is related to its effect on AhR pathway as antagonist/agonist.