Cytochrome P450 1A1 (CYP1A1) plays a key role in the metabolism of carcinogens, such as benzo[a]pyrene (B[a]P) and metabolites to ultimate carcinogens. Three human allelic variants, namely wild-type (CYP1A1.1), CYP1A1.2 (I462V) and CYP1A1.4 (T461N), were coexpressed by coinfection of baculovirus-infected insect cells with human NADPH-P450 reductase. These recombinant enzymes (in microsomal memb...

The Sp1-like family of transcription factors is emerging as an integral part of the cellular machinery involved in the control of gene expression. Members of this family of proteins contain three highly homologous C-terminal zinc-finger motifs that bind GC-rich sequences found in the promoters of a diverse number of genes, such as the basic transcription element (BTE) in the promoter of the car...

Objective: To estimate and compare the frequency of CYP1A1*2A gene polymorphisms in a Brazilian population and determine the possible contribution of these genetic variations to lung cancer risk. Methods: The study population included 200 patients with lung cancer, and the control group consisted of 264 blood donors. Genomic DNA was obtained from peripheral blood samples. The PCR-RFLP method wa...

BACKGROUND Cytochrome P450 (CYP) isoenzymes are an important phase I enzyme system. In the present study, we investigated the effects of Oenanthe javanica (Blume) DC on CYP1A1 and CYP1A2. FINDINGS Whole plants were completely dried and then divided into leaves, stems, and roots for extraction. The human liver hepatocellular carcinoma cell line HepG2 was treated with ethanol extracts of these ...

The age-standardized incidence of esophageal cancer (EC) varies from 3 to >100/100,000 per year in different provinces of Iran. This striking variation of incidence is associated with differences in ethnic backgrounds, raising the possibility that genetic factors are involved in the pathogenesis of EC. We compared the frequencies of polymorphisms in ten genes that have been hypothesized to have...

Human cytochromes P450 1A1 and 1A2 play important roles in drug metabolism and chemical carcinogenesis. Although these two enzymes share high sequence identity, they display different substrate specificities and inhibitor susceptibilities. In the present studies, we investigated the structural basis for these differences with phenacetin as a probe using a number of complementary approaches, suc...

Hypospadias is one of the most common congenital anomalies. Increased exposure to environmental factors (endocrine-disrupting chemicals and smoking) or maternal endogenous estrogen may cause hypospadias because male sexual differentiation is dependent on normal androgen homeostasis. Moreover, interactions between genetic factors and cigarette smoking and other chemicals have been suggested. It ...

Knowledge of the response of cytochrome P450 1B1 (CYP1B1) to exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in both humans and rodents is limited. To improve the analysis of CYP1 proteins, specific CYP1B1 and CYP1A1 polypeptides were expressed as hexahistidine-tagged fusion proteins in Escherichia coli, purified to homogeneity and used to produce polyclonal antibodies in rabbits. Immuno...

Marine mammals can accumulate environmental contaminants in their blubber at concentrations harmful to laboratory animals. Induction of the cytochrome P450 1A1 (CYP1A1) enzyme is widely used as a biomarker of exposure and molecular effects in animal species, yet the validity of this biomarker has not been established in marine mammals. In vivo studies are generally precluded in these protected ...

Complex disease such as cancer results from interactions of multiple genetic and environmental factors. Studying these factors singularly cannot explain the underlying pathogenetic mechanism of the disease. Multi-analytical approach, including logistic regression (LR), classification and regression tree (CART) and multifactor dimensionality reduction (MDR), was applied in 188 lung cancer cases ...