The transcriptional induction of the cytochrome P-450 1A1 (CYP1A1) gene by xenobiotics such as polyaromatic hydrocarbons is dependent on their interaction with the aryl hydrocarbon receptor. Administration of the structurally unrelated compounds metyrapone (a cytochrome P-450 inhibitor) or dexamethasone (a glucocorticoid) to male rats does not induce hepatic CYP1A1 mRNA. However, administration...

The aryl hydrocarbon receptor (AhR), a client protein of heat shock protein 90 (Hsp90), is a ligand-activated transcription factor that plays a role in polycyclic aromatic hydrocarbon (PAH)-induced carcinogenesis. Tobacco smoke activates AhR signaling leading to increased transcription of CYP1A1 and CYP1B1, which encode proteins that convert PAHs to mutagens. Recently, p53 was found to regulate...

The mechanisms involving the inhibitory effects of ascorbic acid (AA) on carcinogenesis have not fully defined, except for its free-radical scavenging activity against oxidative DNA damage. In this study, we examined the effects of AA on the expression of the aryl hydrocarbon receptor (AhR)-regulated gene cytochrome P4501A1 (CYP1A1), which catalyzes the activation of genotoxic metabolites that ...

Cytochrome P450 1A1 (CYP1A1) and 1B1 (CYP1B1) are phase I enzymes, the expression of which can be affected by many environmental compounds, including dioxins and dioxin-like compounds. Because CYP1A1 and CYP1B1 expression can easily be determined in peripheral blood lymphocytes, it is often suggested as biomarker of exposure to these compounds. In this study we investigated the interindividual ...

We recently demonstrated that heavy metals, Hg2+, Pb2+, and Cu2+ induced Cyp1a1 gene expression, yet the mechanisms involved remain unknown. To explore the molecular mechanisms involved in the modulation of Cyp1a1 by heavy metals, Hepa 1c1c7 cells were treated with the metals in the presence and absence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent Cyp1a1 inducer. Time-dependent effec...

Hepcidin is known to be expressed in fish with bacterial challenge and iron overload. Here we first report the hepcidin expression induced in the developmental stages from embryo to fry of red sea bream (Pagarus major) and in juvenile black porgy (Acanthopagrus schlegelii B.) upon continuous waterborne exposure to BaP. The gene expression of CYP1A1 and IgL (immunoglobulin light chain) were both...

Some chemical modulators of cytochrome P4501A1, Cyp1A1, expression also perturb the activity of serine palmitoyltransferase, SPT, a heterodimeric protein responsible for catalyzing the first reaction in sphingolipid biosynthesis. The effect of altered SPT activity on Cyp1A1 expression has generally been attributed to changes in the composition of bioactive sphingolipids, generated downstream in...

Vanadium (V(5+)), a heavy metal contaminant with important toxicological consequences, has received considerable attention as an anticancer agent, although the mechanisms remain unknown. As a first step to investigate these mechanisms, we examined the effect of V(5+) (as ammonium metavanadate, NH(4)VO(3)) on the expression of the aryl hydrocarbon receptor (AhR)-regulated gene: cytochrome P450 1...

background: breast cancer is the first leading cause of cancer-related death in women. pesticides which are excessively used in northern iran are one of the most important risk factors for breast cancer incidence. the cytochrome p450 1a1 (cyp1a1) is a key enzyme in xenobiotics metabolism and snps of its coding gene has been verified to be important in cancer susceptibility. the aim of this stud...

Cytochrome P450 1A1 (CYP1A1) is one of the most important detoxification enzymes due to its broad substrate specificity and wide distribution throughout the body. On the other hand, CYP1A1 can also produce highly carcinogenic intermediate metabolites through oxidation of polycyclic aromatic hydrocarbons. We describe what we believe to be a novel regulatory system for whole-body CYP1A1 expressio...