Search results for "Aryl Hydrocarbon"
showing 10 items of 77 documents
Vertical distribution of AhR-activating compounds in sediments contaminated by modernized pulp and paper industry
2013
Increased ethoxyresorufin-O-deethylase (EROD) activity is a sensitive biomarker of exposure to the chemicals which activate the aryl hydrocarbon receptor (AhR) and induce the cytochrome P450 system, such as many polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs). Pulp bleaching was one of the main sources of PCDDs and PCDFs until elemental chlorine free (ECF) and total chlorine free bleaching processes since 1990s have remarkably decreased but not completely eliminate discharges of these chemicals. In addition, historically contaminated sediments may act as a source of these persistent contaminants. In this study, the contam…
The aryl hydrocarbon receptor-dependent deregulation of cell cycle control induced by polycyclic aromatic hydrocarbons in rat liver epithelial cells
2006
Disruption of cell proliferation control by polycyclic aromatic hydrocarbons (PAHs) may contribute to their carcinogenicity. We investigated role of the aryl hydrocarbon receptor (AhR) in disruption of contact inhibition in rat liver epithelial WB-F344 'stem-like' cells, induced by the weakly mutagenic benz[a]anthracene (BaA), benzo[b]fluoranthene (BbF) and by the strongly mutagenic benzo[a]pyrene (BaP). There were significant differences between the effects of BaA and BbF, and those of the strongly genotoxic BaP. Both BaA and BbF increased percentage of cells entering S-phase and cell numbers, associated with an increased expression of Cyclin A and Cyclin A/cdk2 complex activity. Their eff…
Chronic exposure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces an obesogenic effect in C57BL/6J mice fed a high fat diet
2017
IF 3.582; International audience; Contaminant involvement in the pathophysiology of obesity is widely recognized. It has been shown that low dose and chronic exposure to endocrine disruptor compounds (EDCs) potentiated diet- induced obesity. High and acute exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a persistent organic pollutant (POP) and an EDC with anti-estrogenic property, causes wasting syndrome . However at lower doses, the TCDD metabolic effects remain poorly understood. We investigated the obesogenic effect during chronic exposure of TCDD at 1μg/kg body weight (bw)/week in adult C57BL/6J mice fed with a high fat diet (HFD) and exposed from 10 to 42 weeks old to TCDD or e…
CYP2C8 gene polymorphism and bisphosphonate-related osteonecrosis of the jaw in patients with multiple myeloma
2011
Osteonecrosis of the jaw is an uncommon but potentially serious complication of bisphosphonate therapy in multiple myeloma. Previous studies showed that the presence of one or two minor alleles of the cytochrome P450, subfamily 2C polypeptide 8 gene (CYP2C8) polymorphism rs1934951 was an independent prognostic marker associated with development of osteonecrosis of the jaw in multiple myeloma patients treated with bisphosphonates. The aim of this study was to validate the frequency of SNP rs193451 in 79 patients with multiple myeloma. In 9 (22%) patients developing osteonecrosis of the jaw, a heterozygous genotype was found, in contrast with those who did not develop osteonecrosis of the jaw…
Endogenous AhR agonist FICZ accumulates in rainbow trout (Oncorhynchus mykiss) alevins exposed to a mixture of two PAHs, retene and fluoranthene
2022
AbstractMultiple studies have reported synergized toxicity of PAH mixtures in developing fish larvae relative to the additive effect of the components. From a toxicological perspective, multiple mechanisms are known to contribute to synergism, such as altered toxicodynamics and kinetics, as well as increased oxidative stress. An understudied contributor to synergism is the accumulation of endogenous metabolites, for example: the aryl hydrocarbon receptor 2 (AhR2) agonist and tryptophan metabolite 6-Formylindolo(3,2-b)carbazole (FICZ). Fish larvae exposed to FICZ, alongside knock-down of cytochrome p450 (cyp1a), has been reported to induced symptoms of toxicity similar to those observed foll…
Genetics of the variable expression of CYP3A in humans.
2004
CYP3A isozymes participate in the metabolism of 45-60% of currently used drugs and of a variety of other compounds such as steroid hormones, toxins, and carcinogens. The CYP3A expression status is a major determinant of drug efficacy and safety, and it may also affect an individual's predisposition to certain cancers. The inter- and intraindividual expression of CYP3A is variable because of a complex interplay between genetic and environmental factors. Markers predictive of the individual CYP3A activity could improve therapies with CYP3A substrates by personalised dose adjustments, but their development has been slower than for other drug-metabolizing enzymes. Here we summarize the recent p…
Enzymic control of irreversible binding of metabolically activated benzo(a)pyrene in perfused rat liver by monooxygenase activity.
1977
Addition of [3H]-benzo(a)pyrene to the perfusion medium of isolated rat livers results in irreversible binding of radioactivity to DNA, RNA and protein. Binding to DNA accounted for about 0.1% of the total radioactivity which was bound in livers from animals treated with oil or saline and was increased by a factor of 3–5 after pretreatment of the animals with β-naphthoflavone or with phenobarbital. When the inhibitiors of monooygenase activity, α-naphthoflavone or metyrapone, were present in the perfusion medium, irreversible binding was reduced in livers from both β-naphthoflavone- and phenobarbital-pretreated animals, irrespective of the inhibitor used.
The Val432Leu polymorphism of the CYP1B1 gene is associated with differences in estrogen metabolism and bone density.
2009
Polymorphisms of the CYP450 genes that encode for the enzymes that metabolize estrogen are linked to hormone-related cancers. We investigated the impact of two polymorphisms of the CYP1B1 gene previously reported to be associated with hormone-related disorders on estrogen metabolism and bone mineral density (BMD), another hormone-dependent condition, in women from different ethnic backgrounds. Four hundred sixty-eight postmenopausal Caucasian women, 220 from St. Louis, MO, USA (mean age=63.5+/-0.53 years) and 248 from Palermo, Italy (mean age=72.9+/-0.44 years) participated in the study. Measurements of urinary estrogen metabolites by enzyme-linked immunoassay, serum estradiol by ultrasensi…
Global and sex-specific epigenome-wide association studies for the identification of the main methylated loci related to smoking in a mediterranean p…
2019
Abstract Background Tobacco use has been reported to be the main cause of 90% of male and 80% of female lung cancers, as well as a relevant risk factor for other cancers such as oropharynx, larynx, esophagus, stomach, liver, pancreas, kidney, bladder, and colorectum. Smoking directly affects DNA methylation and although several genes have been reported to be differentially methylated in smokers, gender differences and population-specific differences remain to be further investigated. Our aim was to undertake global and sex-specific genome-wide epigenomic studies (EWAS) in a Mediterranean population to identify the main smoking DNA-methylated genes. Methods We analyzed 88 participants in the…
Transcriptional profiling of rat white adipose tissue response to 2,3,7,8-tetrachlorodibenzo-ρ-dioxin
2015
Polychlorinated dibenzodioxins are environmental contaminants commonly produced as a by-product of industrial processes. The most potent of these, 2,3,7,8-tetrachlorodibenzo-rho-dioxin (TCDD), is highly lipophilic, leading to bioaccumulation. White adipose tissue (WAT) is a major site for energy storage, and is one of the organs in which TCDD accumulates. In laboratory animals, exposure to TCDD causes numerous metabolic abnormalities, including a wasting syndrome. We therefore investigated the molecular effects of TCDD exposure on WAT by profiling the transcriptomic response of WAT to 100 mu g/kg of TCDD at 1 or 4 days in TCDD-sensitive Long-Evans (Turku/AB; L-E) rats. A comparative analysi…