• Title/Summary/Keyword: CYP1A1 gene

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Tissue-Specific Splicing and Expression of Cyp1A1 in the Liver and Brain of Offspring Rats after Gestational Exposure to 2,3,7,8-Tetrachlorodibenzo-P-Dioxin

  • Lim, Hak-Seob;Lee, Chul-Won;Kim, Yong-Hoon;Joo, Woo-Hong;Yong-Kweon;Moon, Ja-Young
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2003.10b
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    • pp.190-191
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    • 2003
  • We investigated the effects of gestational and lactational exposures to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the differential induction of CYP1A1 in the levels of protein and gene expression in the liver and brain regions of offspring rats. For this study, pregnant Sprague Dawley rats were orally exposed to TCDD (1 or 10 ng/kg body weight/day) starting at Day 1 of gestation up to Day 20 of postpartum. (omitted)

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Bioassays of Polycyclic Aromatic Hydrocarbons in ZR-75-1 Human Breast Cancer Cells

  • Min, Kyung-N.;Sheen, Yhun-Y.
    • Environmental Mutagens and Carcinogens
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    • v.23 no.1
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    • pp.35-40
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    • 2003
  • Polycyclic aromatic hydrocarbons (PAH) are frequently detected in food, water, soil, and sediment and are widespread environmental pollutants formed by the incomplete combustion of fossil fuels, woods and other organic matter. PAHs are considered to be probable human carcinogens. The mechanism of action of PAHs has been studied extensively, however it is not clear how PAHs turn on CYP1A1 in human breast cancer. Our laboratory have been studied the effect of PAHs in the human breast cancer cell MCF7. In this study, we examined the ZR-75-1 human breast cancer cells as a new system to evaluate bioactivity of PAHs. ZR-75-1 human breast cancer cell line responses to estrogen and progesteron. We have been able to estbilish long term culture system of this cells then used for the study to observe the effect of PAHs. We demonstrate that PAHs induced the CYP1A1 promoter and 7-ethoxyresolufin O-deethylase (EROD) activity in a concentration-dependant manner. RT-PCR analysis indicated that PAHs significantly up-regulate the level of CYP1A1 mRNA. Some of PAHs showed stronger stimulatory effect on CYP1 gene expression than TCDD. Apparently, ZR-75-1 cells have Aryl hydrocarbon receptors, therefore it would be good experimental tool to study the cross-talk between PAHs and steroid actions.

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The effect of PAHs on the regualtion of CYP1 gene in ZR-75-1 and MCF7 human breast cancer cells

  • Min, K.N.;Sheen, Yhun Y.;Kim, J.Y.;Cho, M.J.
    • Proceedings of the Korea Society of Environmental Toocicology Conference
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    • 2003.05a
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    • pp.193-193
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    • 2003
  • Recent industrial society has human widely exposed to PAHs that are coming from the incomplete combustion of organic material as widespread environmental contaminants. Biological activities of PAHs are not known although PAHs are considered as carcinogens. The mechanism of action of PAHs has been studied extensively, however it is not clear how PAHs turn on CYPlAl in human breast cancer, Our laboratory have been studied the effect of PAHs in the human breast cancer cells, MCF-7. In this study, we examined the ZR-75-1, human breast cancer cells, as a new system to evaluate bioactivity of PAHs and to compare the PAHs action with that of MCF-7 cells. ZR-75-1 human breast cancer cell line is responsible to estrogen and progesterone. We have been able to establish long term culture system of this cells then used for the study to the effect of 13 different PAHs and environmental samples. We demonstrate that PAHs induced the CYP1A1 promoter and 7-ethoxyresorufin O-deethylase (EROD) activity in a concentration-dependent manner. RT-PCR analysis indicated that PAHs significantly up-regulate the level of CYP1A1 mRNA. Some of PAHs showed stronger stimulatory effect on CYP1 gene expression than TCDD Apparently, ZR-75-1 cells have Aryl hydrocarbon receptors (AhR), therefore it would be a good experimental tool to study the cross-talk between PAHs and steroid actions.

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Transcriptional Modulation of Metabolism-Related Genes in Brackish Water Flea Diaphanosoma celebensis Exposed to Mercury (수은 노출에 따른 기수산 물벼룩의 대사 관련 유전자의 발현 양상)

  • Min Jeong, Jeon;Je-Won, Yoo;Young-Mi, Lee
    • Journal of Marine Life Science
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    • v.7 no.2
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    • pp.145-153
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    • 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.

Susceptibility of Lung Cancer with Polymorphisms of CYP1A1, GSTM1, GSTM3, GSTT1 and GSTP1 Genotypes in the Population of Inner Mongolia Region

  • Jiang, Xue-Yan;Chang, Fu-Hou;Bai, Tu-Ya;Lv, Xiao-Li;Wang, Min-Jie;Wang, Guang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.13
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    • pp.5207-5214
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    • 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.

Regulation of CYP 1A1 gene expression by retinoic acid receptor, retinoid X receptor and constitutive androstane receptor in rainbow trout hepatoma cells(RTH 149)

  • Kim, Ji-Sun;Yang, So-Yeun;Seo, Mi-Jung;Sheen, Yhun-Yhong
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.119.2-119.2
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    • 2003
  • Exposure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes a variety of biological and toxicology effects, most of which are mediated by aryl hydrocarbon receptor (AhR). The ligand-bound AhR as a heterodimer with AhR nuclear translocator (ARNT) binds to its specific DNA recognition site, the dioxin-responsive element (DRE), and it results in increased transcription of CYP1A1 gene. Retinoic acid (RA) regulates the transcription of various genes for several essential functions through binding to two classes of nuclear receptors, the retinoic acid receptor (RAR) and retinoid X receptor (RXR). (omitted)

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Anti-proliferating Effects and Gene Expression Profiles through Antioxidant Activity of Porphyra yezoensis Fractions on Human HepG2 Cell Lines (인간 간암세포주 HepG2에서 김 분획물의 항산화 활성을 통한 증식 억제 및 유전자 발현 양상)

  • Oh, Youn Jeong;Kim, Jung Min;Bang, In Seok
    • Journal of Life Science
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    • v.28 no.2
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    • pp.176-186
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    • 2018
  • In this study, the total polyphenol contents, antioxidant activities and anti-proliferation effects of HepG2 cell lines in organic slovent fractions obtained from the main methanolic extract of P. yezoensis were analyzed. The polyphenol content of the $CHCl_3$ fraction was $10.3{\mu}g/mg$, slightly less than $13.08{\mu}g/mg$ of the water fraction, but $ED_{50}$ estimated by measuring DPPH free radical scavenging activity exhibited the highest $16.96{\mu}g/ml$ in the $CHCl_3$ fraction. The proliferation effects of $CHCl_3$ and EtOAc fraction toward HepG2 cells inhibited in a dose-dependent manner, showed 90% inhibition when treated for 24 hr at $900{\mu}g/ml$ of $CHCl_3$ fraction. Meanwhile gene expression patterns in HepG2 cells treated $50{\mu}g/ml$ of $CHCl_3$ fraction were identified with microarray analysis. Concerning the efficacy of P. yezoensis, gene ontology analysis explored the genes associated with response to molecule of bacterial origin, vitamin D metabolic process, and response to nutrient. Thus IL6R, CYP1A1 were selected as significant genes based on expression patterns of HepG2 cells, and pathway analysis indicates that ARNT might be considered as a upstream regulator. Also, expression analysis of IL6R and CYP1A1, activity of upstream regulator ARNT in HepG2 cells was confirmed based on Western blotting analysis at the protein level after being treated with 50 and $100{\mu}g/ml$ of $CHCl_3$ fraction.