Polycyclic aromatic hydrocarbons (PAHs) induce cytochrome P-450 monoxygenase enzymes that catalyze the formation of DNA adducts. We investigated the effects benzo(α)pyrene (B[α]P) alone or in combination with ethanol on normal human keratinocyte (NHK) growth, induction of cytochrome P-4501A1 (CYP1A1), and modulation of these treatments by retinoic acid (RA) in a serum-free culture medium. Growt...

Induction of cytochrome P4501A1 (CYP1A1) in the hepatoma Hepa1c1c7 cell line results in an elevation in the excretion rate of 8-oxoguanine (oxo8Gua), a biomarker of oxidative DNA damage and the major repair product of 8-oxo-2'-deoxyguanosine (oxo8dG) residues in DNA. Treatment of this cell line with 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD), a nonmetabolized environmental contaminant, and indo...

BACKGROUND The Cytochrome P-4501A1 (CYP1A1) gene, located on chromosome 15q, is involved in the metabolism of carcinogens mainly polycyclic aromatic hydrocarbons as well as estrogen. It is considered as candidate gene for low-penetrance breast cancer susceptibility. Hence the present study aims to discuss the role of CYP1A1 polymorphisms in breast cancer. MATERIALS AND METHODS A total of 250 ...

We previously demonstrated that Peganum harmala L. extract and its main active constituents, harmine and harmaline inhibit the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated induction of the carcinogen-activating enzyme, Cyp1a1, in vitro. However, the effect of both alkaloids on Cyp1a1 in vivo has not been investigated. Therefore, the aim of this study is to examine the effect of harmine a...

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants; a number are carcinogenic. Metabolic polymorphisms may modulate susceptibility to PAH-induced DNA damage and carcinogenesis. This study investigates the relationship between PAH-DNA adduct levels (in maternal and newborn WBCs) and two polymorphisms: (a) an MspI RFLP in the 3' noncoding region of cytochrome P4501A1 ...

Procarcinogenic polycyclic aromatic hydrocarbons (PAHs) induce their own metabolism and activation by binding to the cytosolic aryl hydrocarbon receptor (AhR), which then translocates to the nucleus and activates CYP1A1 gene transcription via xenobiotic response elements (XREs). Although the AhR demonstrates a strict specificity for planar aromatics, nonplanar (+/-)-trans-7,8-dihydroxy-7,8-dihy...

We investigated CYP1A1*2A, CYP1A1*2C, CYP1A2*1C, CYP1A2*1F, GSTM1 and NAT2 gene polymorphisms, involving enzymes which metabolize many carcinogens, with reference to colorectal cancer risk. The distribution of these genotypes was not associated with risk overall. However, the CYP1A1*2A T/C genotype showed a significant association with colorectal cancer risk in never-smokers (odds ratio [OR], 3...

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 ...

The purpose of the present experiments was to examine dose-response relationships for induction of hepatic mRNA following a single administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to rats. The induction of cytochrome P450-1A1 (CYP1A1) mRNA is compared to other "dioxin-responsive" genes including UDP-glucuronosyltransferase I, plasminogen activator inhibitor 2, and transforming growt...

Indoxyl sulfate (IS) induces fibrosis and inflammation in kidneys via oxidative stress through the induction of transforming growth factor-β1 (TGF-β1) and monocyte chemotactic protein-1 (MCP-1). Furthermore, IS is a potent endogenous agonist for aryl hydrocarbon receptor (AHR), which regulates the transcription of genes such as cytochrome P450 (CYP) 1A1. Indole-3-propionic acid (IPA) is an anti...