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 thi...

Heme metabolism normally involves enzymatic conversion to biliverdin and subsequently to bilirubin, catalyzed by heme oxygenase and biliverdin reductase, respectively. We examined the ability of exogenously added hemin, biliverdin, or bilirubin to regulate Cyp1a1, an enzyme that may be active in bilirubin elimination. A substantial dose-dependent increase in Cyp1a1 mRNA occurred after treatment...

Polymorphisms for genes encoding the metabolic enzymes cytochrome P450 1A1 (CYP1A1) might contribute to the variability in individual susceptibility to lung cancer. The role of CYP1A1 in lung carcinogenesis might be more important at low levels of exposure to carcinogens. In our study, CYP1A1 gene polymorphisms were investigated in healthy subjects and lung cancer patients in Turkish population...

Cigarette smoking has been related to increased risk of colorectal adenomas, but the underlying mechanisms are unknown. Genetic polymorphisms are known for enzymes involved in the activation of polycyclic aromatic hydrocarbons and other tobacco-related carcinogens. Polycyclic aromatic hydrocarbons are activated by cytochrome P4501A1 (CYP1A1) and detoxified by glutathione S-transferases. We inve...

The aim of this study was to investigate the actions of two isomers of DDT (p,p'-DDT, o,p'-DDT) and DDE (p,p'-DDE, o,p'-DDE) on the human placenta. We studied the effects of DDT and its metabolite DDE on CYP1A1 activity and on CYP1A1 and aryl hydrocarbon receptor (AhR) protein expression in placental cells. We used explants from third-trimester human placental tissue and JEG-3 cells, which are ...

Associations of GSTT1, GSTM1 and CYP1A1 gene variants with risk of developing oral cancer were evaluated in this study. A case-control study was conducted in Pashtun population of Khyber Pakhtunkhwa province of Pakistan in which 200 hospital based oral cancer cases and 151 population based healthy controls exposed to similar environmental conditions were included. Sociodemographic data were obt...

Previous studies by us and others have shown a significantly higher level of aromatic DNA adducts in normal adjacent breast tissue samples obtained from breast cancer patients than in those obtained from non-cancerous controls. The increased amount of DNA damage could be related to excess environmental carcinogen exposure and/or genetic susceptibility to such exposure. In the current study, we ...

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...

AIMS We investigated the mechanisms of shear stress (SS)-induced activation of cytochrome P450 (CYP) 1A1 and cell cycle arrest with regard to the role of the aryl hydrocarbon receptor (AhR), since AhR mediates the expression of CYP1A1 induced by polycyclic aromatic hydrocarbons (PAHs) and is thought to be involved in the regulation of cell growth and differentiation. METHODS AND RESULTS Human...

2-(4-Amino-3-methylphenyl)benzothiazole (DF 203, NSC 674495) is a candidate antitumor agent with potent and selective activity against human-derived tumor cell lines in vitro and in vivo. Only sensitive cell lines (e.g., MCF-7) were able to accumulate and metabolize DF 203, forming the main inactive metabolite, 2-(4-amino-3-methylphenyl)-6-hydroxybenzothiazole (6-OH 203). Selective metabolism m...