• Animal Bioscience
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• v.34 no.2
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• pp.312-319
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• 2021

Objective: Stress-induced cytotoxicity caused by xenobiotics and endogenous metabolites induces the production of reactive oxygen species and often results in damage to cellular components such as DNA, proteins, and lipids. The cytochrome P450 (CYP) family of enzymes are most abundant in hepatocytes, where they play key roles in regulating cellular stress responses. We aimed to determine the effects of the antioxidant compound, methylsulfonylmethane (MSM), on oxidative stress response, and study the cytochrome P450 family 3 subfamily A (CYP3A) gene expression in fetal horse hepatocytes. Methods: The expression of hepatocyte markers and CYP3A family genes (CYP3A89, CYP3A93, CYP3A94, CYP3A95, CYP3A96, and CYP3A97) were assessed in different organ tissues of the horse and fetal horse liver-derived cells (FHLCs) using quantitative reverse transcription polymerase chain reaction. To elucidate the antioxidant effects of MSM on FHLCs, cell viability, levels of oxidative markers, and gene expression of CYP3A were investigated in H2O2-induced oxidative stress in the presence and absence of MSM. Results: FHLCs exhibited features of liver cells and simultaneously maintained the typical genetic characteristics of normal liver tissue; however, the expression profiles of some liver markers and CYP3A genes, except that of CYP3A93, were different. The expression of CYP3A93 specifically increased after the addition of H2O2 to the culture medium. MSM treatment reduced oxidative stress as well as the expression of CYP3A93 and heme oxygenase 1, an oxidative marker in FHLCs. Conclusion: MSM could reduce oxidative stress and hepatotoxicity in FHLCs by altering CYP3A93 expression and related signaling pathways.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2647-2653
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• 2012

Involvement of cytochrome P450 genes (CYPs) in breast cancer (BCa) may differ between populations, with expression patterns affected by tumorigenesis. This may have an important role in the metabolism of anticancer drugs and in the progression of cancer. The aim of this study was to determine the mRNA expression patterns of four cytochrome P450 genes (CYP2W1, 3A5, 4F11 and 8A1) in Mexican women with breast cancer. Real-time PCR analyses were conducted on 32 sets of human breast tumors and adjacent non-tumor tissues, as well as 20 normal breast tissues. Expression levels were tested for association with clinical and pathological data of patients. We found higher gene expression of CYP2W1, CYP3A5, CYP4F11 in BCa than in adjacent tissues and only low in normal mammary glands in our Mexican population while CYP8A1 was only expressed in BCa and adjacent tissues. We found that Ki67 protein expression was associated with clinicopathological features as well as with CYP2W1, CYP4F11 and CYP8A1 but not with CYP3A5. The results indicated that breast cancer tissues may be better able to metabolize carcinogens and other xenobiotics to active species than normal or adjacent non-tumor tissues.

• Clinical and Experimental Reproductive Medicine
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• v.32 no.2
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• pp.171-176
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• 2005

Objective: To investigate whether polymorphism of CYP19 gene is associated with the risk of advanced endometriosis in Korean women. Methods: Blood samples were collected from 202 endometriosis patients and 221 controls. The patients with endometriosis of stages III and IV diagnosed by both pathologic and laparoscopic findings to according modified AFS classification. The women undergoing laparoscopic surgery or laparotomy for non-malignant lesions were included in the control group. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) of PCR products were done to determine all individuals' genotype. Results: The heterozygous allele in CYP19 gene was the most common genotypes in both endometriosis and healthy control groups (52.0% vs. 46.1%). CYP19 gene polymorphisms did not show the significant differences between the control group and endometriosis group. Conclusion: The results suggested that the CYP19 genetic polymorphism was not associated with a risk of advanced endometriosis in Korean women.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.6
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• pp.2861-2866
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• 2016

It is thought that population characteristics of breast cancer may be due to a variation in the frequency of different alleles of genes such as CYP1B1. We aimed to determine the association of CYP1B1 polymorphisms in 200 breast cancer cases and 40 controls by PCR-RFLP. Frequencies were assessed with clinical and risk factors in Egyptian patients. The genotype LV and the Leu allele frequencies for patients and controls were 42.9% and 50%, and 52.9% and 53.3%, respectively), with no significant differences observed (P values = 0.8 and 0.6, respectively). There was also no significant association between genotypes and any risk factors for cases (P>0.05) except laterality and metastasis of the tumor (P values=0.006 and 0.06, respectively). The CYP1B1 polymorphism Val432Leu was not associated with breast cancer in Egypt, but may provide clues for future studies into early detection of the disease.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1757-1760
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• 2012

Breast cancer is a major cause of death in women worldwide. Mammary tissue expressing xenobiotic metabolizing enzymes metabolically activate or detoxify potential genotoxic breast carcinogens. Deregulation of these xenobiotic metabolizing enzymes is considered to be a major contributory factor to breast cancer. The present study is focused on the expression of the xenobiotic metabolizing gene, CYP1A1, in breast cancer and its possible relationships with different risk factors. Twenty five tumors and twenty five control breast tissue samples were collected from patients undergoing planned surgery or biopsy from different hospitals. Semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and western-blotting were used to investigate the expression of CYP1A1 in breast cancer control and disease samples. mRNA expression of CYP1A1 was down-regulated in 40% of breast tumor samples. Down-regulation was also observed at the protein level. Significnat relations were noted with marital status and tumour grade but not histopathological type. In conclusion, CYP1A1 protein expression was markedly reduced in tumor breast tissues samples as compared to paired control tissue samples.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2003.10a
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• pp.181-181
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• 2003

We have studied the mechanism of action of TCDD on CYP1A1 promoter activity in both Hepa Ⅰ and MCF-7 cells using transient transfection system with p1A1-Luc reporter gene. When HDAC inhibitors, such as trichostatin A, HC toxin and a novel HDAC inhibitor, IN2001 were cotreated with TCDD to the cells transfected with plAt-Luc reporter gene, the basal promoter activity of CYP1A1 was increased by HBAC inhibitors. Also, in MCF-7 human breast cancer cells, HDAC inhibitors, such as IN2001 and trichostatin A increased the basal activity of CYP1A1 promoter but TCDD stimulated CYP1A1 promoter activity was not changed by HDAC inhibitors. And, in stably-transfected Hepa Ⅰ cells with p1A1-Luc, HDAC inhibitors increased the basal promoter activity only Also, we have investigated the effects of HDAC inhibitors on the human breast and prostate cancer cells in terms of cell proliferation and apoptosis based on SRB assay. IN2001 as well as trichostatin A inhibited the MCF-7, MDA-MB-231, MDA-MB-468, T47D, ZR75-1, PC3 cell growth dose-dependently. The growth inhibition of these cells with HDAC inhibitors was associated with profound morphological change, which suggests the HDAC inhibitors induced apoptosis of cells. The result of cell cycle analysis after 24h exposure of IN2001 showed G2/M cell cycle arrest in MCF-7 cells and apoptosis in T47D and MDA-MB-231 cells.

• Parasites, Hosts and Diseases
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• v.49 no.1
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• pp.45-49
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• 2011

Chemotherapy of clonorchiasis with praziquantel (PZQ) is effective but about 15% of treated cases have been reported uncured. The present study investigated correlation of single nucleotide polymorphisms (SNPs) of the cytochrome P450 gene, CYP3A5 and cure of clonorchiasis. A total of 346 egg passing residents were subjected and treated by 3 doses of 25 mg/kg PZQ. Reexamination recognized 33 (9.5%) uncured and 313 cured. Numbers of eggs per gram of feces (EPGs) before treatment were significantly lower in the cured group than in the uncured group ($2,011.2{\pm}3,600.0$ vs $4,998.5{\pm}7,012.0$, P<0.001). DNAs of the subjects were screened for SNPs at 7 locations of CYP3A5 using PCR. In the uncured group, the SNP frequencies at g.-20555G > A and g.27526C > T of CYP3A5 were 15.2% and 9.1% while those were 3.8% and 1.0%, respectively, in the cured group. The cure rate was Significantly lower in the cases with SNP at g.27526C > T and EPGs ${\geq}$ 1,000. In conclusion, EPGs and SNPs of CYP3A5 are factors which influence cure of clonorchiasis by PZQ therapy. It is strongly suggested to recommend 2-day medication for individuals with high EPGs ${\geq}$ 1,000.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6715-6720
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• 2014

The purpose of this study was to evaluate associations of the CYP1A1 gene variant rs4646903 polymorphism with the risk of developing esophageal cancer (EC). A case-control study was carried out in Pashtun population of Khyber Pakhtunkhwa province of Pakistan in which 140 hospital based EC cases and 196 population based healthy controls exposed to similar environmental conditions were included. A specific method based on the real time polymerase chain reaction (RT-PCR) was used to detect genotypes in case and control groups and results were then analyzed with SPSS version 20. In our population, individuals with CC and TC genotypes of the CYP1A1 rs4646903 polymorphism had significantly higher risk of EC (adjusted odds (OR): 15.709, 95%CI: 6.065-40.686, OR: 3.256 95%CI: 1.902-5.574 respectively). The 'C' allele was strongly associated with the disease (p< 0.0001). Adjusted OR was higher (1.5 times in C/C) in case of variant alleles that show the contribution of environmental and nutritional factors towards the development of EC. Our findings suggest that presence of the 'C' allele of rs4646903 (T>C) may be one of the risk alleles for EC susceptibility in Pashtun population.

• Journal of Pharmacopuncture
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• v.14 no.3
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• pp.63-69
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• 2011

Objectives : The purpose of this study is to evaluate the effect of Artemisia capillaries on gene expression of lipid metabolism in rats. Methods : The author performed several experimental items to analyze the total cholesterol and triglyceride in liver tissue, the gene expressions of CYP7A1 and HMG-CoA reductase. Results : 1. In Artemisia capillaries group, the levels of total cholesterol in liver tissue were significantly decreased. 2. In Artemisia capillaries group, the ratios of CYP7A1, HMG-CoA reductase were as same as the normal group. Conclusions : From the above results, Artemisia capillaries can be used to treat hyperlipidemia.

• Environmental Mutagens and Carcinogens
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• v.24 no.1
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• pp.40-45
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• 2004

In order to understand the mechanism of the regulation of drug metabolizing enzyme gene expression, we have studied the induction of CYP1A1 and GSTα, μ, π enzymes in Japanese monkey and rhesus monkey after the treatment with 3-methylcholanthrene (3MC) and di-n- butyl phthalate (DBP) and bisphenol A (BPA). The levels of mRNA were measured_by RT-PCR in brain, intestine and liver. In the case of adult monkey, treatment with 3MC induced CYP1A1 mRNA in brain by 2-fold. The treatment with DBP induced CYP1A1 mRNA. Effects of 3MC and DBP on GST mRNA expression was not clear. But GSTμ was slightly inhibited by the treatment with 3MC and DBP. GSTα was not induced by the treatment with 3MC and DBP in brain. GSTπ was slightly induced by the treatment with 3MC and DBP in brain. In the case of fetus monkey, the basal levels of fetus CYP1A1 mRNA and GSTs mRNA were relatively low compared to adult monkey. As the age of monkey increased, the basal levels of CYP1A1 mRNA were also increased. 3MC induced the expression of CYP1A1 mRNA in liver, whereas it didn't significantly induce CYP1A1 mRNA in brain. The levels of GSTμ and GSTα were not changed by the treatment with 3MC and DBP. GSTπ was slightly induced by the treatment with 3MC and DBP.