CYP1A1

In vitro systems are useful tools for unravelling species differences in xenobiotic metabolism.The current work aimed to validate the technique of precision-cut liver slices (PCLS) for comparative studies on xenobiotic metabolism in swine and cattle.PCLS from swine (n = 3) and cattle (n = 3) were produced using a Brendel-VitronTM Tissue Slicer and cultured for 6 h. Tissue viability was preserved throughout the whole culture period.Metabolic viability was evaluated using the anthelmintics albendazole (ABZ) and fenbendazole (FBZ) as model drugs, as well as other substrates of hepatic monooxygenases: benzydamine (BZ) N-oxygenase (FMO-dependent), and the O-dealkylations of 7-ethoxyresorufin (EROD, CYP1A1-dependent) and 7-methoxyresorufin (MROD, CYP1A2-dependent)...

Lung cancer is the leading cause of cancer death worldwide. Polycyclic aromatic hydrocarbons (PAHs) are metabolized by the cytochrome P450 (CYP)1A and 1B1 to DNA-reactive metabolites, which could lead to mutations in critical genes, eventually resulting in cancer. Omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial against cancers. In this investigation, we elucidated the mechanisms by which omega-3 fatty acids EPA and DHA will attenuate PAH-DNA adducts and lung carcinogenesis and tumorigenesis mediated by the PAHs BP and MC...

Aryl hydrocarbon receptor (AHR) signalling integrates biological processes that sense and respond to environmental, dietary, and metabolic challenges to ensure tissue homeostasis. AHR is a transcription factor that is inactive in the cytosol but upon encounter with ligand translocates to the nucleus and drives the expression of AHR targets, including genes of the cytochrome P4501 family of enzymes such as Cyp1a1. To dynamically visualise AHR activity in vivo, we generated reporter mice in which firefly luciferase (Fluc) was non-disruptively targeted into the endogenous Cyp1a1 locus...

We investigated possible associations between the internal concentrations of POPs and correlations between blood and tumor tissue concentrations in patients who underwent surgery for breast cancer and breast reduction as controls. Genetic variations in CYP1A1, GSTP1, GSTM1, and GSTT1 and hOGG1 were evaluated to determine whether they represent risk factors for breast cancer. Certain POPs have been found to be associated with breast cancer development. GST-P1 polymorphism represented a significant risk for breast cancer with unadjusted OR...

Human activities have directly impacted the environment, causing significant ecological imbalances. From the different contaminants resulting from human activities, plastics are of major environmental concern. Due to their high use and consequent discharge, plastics tend to accumulate in aquatic environments. There, plastics can form smaller particles (microplastics, MPs), due to fragmentation and weathering, which are more prone to interact with aquatic organisms and cause deleterious effects, including at the basis of different food webs...

INTRODUCTION: Metal oxide nanoparticles are currently used widely in many aspects of human and animal life with broad prospects for biomedical purposes. The present work was carried out to investigate the effects of orally administrated TiO2NPs, ZnONPs, IONs and Al2 O3 NPs on the mRNA expression level of CYP 1A1 and NBN in the rat liver. MATERIALS AND METHODS: Four groups of male Albino rats were given their respective treatment orally for 60 days in a dose of 1/20 of the LD50 TiO2NPs (600 mg/Kg b...

The use of disinfectants, such as Sodium Dodecylbenzene Sulfonic acid salt (SDBS), has grown since the SARS-CoV-2 pandemic, with environmentally unknown consequences. The present study analyzed SDBS effects in the fish species Danio rerio, using a combination of biomarkers. Our data reported that larvae had their total locomotor activity increased when exposed to 1mg/L of SDBS, but this parameter was decreased in fish exposed to 5mg/L. A significant increment of erratic movements was reported in fish exposed to 1 and 5mg/L of SDBS...

BACKGROUND: Cytochrome P450 (CYP) comprises a group of phase-I metabolizing enzymes that are important in xenobiotics metabolism. Genetic polymorphism of CYPs has been comprehensively studied for their association with a range of diseases. In this study, we assessed single-nucleotide polymorphism (SNP) of CYP1A, CYP1B, CYP2B, and CYP2C and their role in gastrointestinal (GI) cancer susceptibility in the rural population of Maharashtra. MATERIALS AND METHODS: In this hospital-based case-control study, the association of polymorphism of CYP genes was studied by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method...

Inhalation exposure to plastic incineration emissions (PIEs) is a problem of increasing human relevance, as plastic production and waste creation have drastically increased since mainstream integration during the 20th century. We investigated the effects of PIEs on human nasal epithelial cells (HNECs) to understand if such exposures cause damage and dysfunction to respiratory epithelia. Primary HNECs from male and female donors were cultured at air-liquid interface (ALI), and 16HBE cells were cultured on coverslips...

The cytochrome P450 1A (CYP1A) subfamily of xenobiotic metabolizing enzymes (XMEs) consists of two different isoforms, namely CYP1A1 and CYP1A2, which are highly conserved among species. These two isoenzymes are involved in the biotransformation of many endogenous compounds as well as in the bioactivation of several xenobiotics into carcinogenic derivatives, thereby increasing the risk of tumour development. Cattle (Bos taurus) are one of the most important food-producing animal species, being a significant source of nutrition worldwide...

Exposure to triclocarban (TCC), a commonly used antibacterial agent, has been shown to induce significant intestine injuries and colonic inflammation in mice. However, the detailed mechanisms by which TCC exposure triggered enterotoxicity remain largely unclear. Herein, intestinal toxicity effects of long-term and chronic TCC exposure were investigated using a combination of histopathological assessments, metagenomics, targeted metabolomics, and biological assays. Mechanically, TCC exposure caused induction of intestinal aryl hydrocarbon receptor (AhR) and its transcriptional target cytochrome P4501A1 ( Cyp1a1 ) leading to dysfunction of the gut barrier and disruption of the gut microbial community...

An ethanol extract of Piper auritum leaves (PAEE) inhibits the mutagenic effect of three food-borne aromatic amines (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP); 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx); 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) in the TA98 Salmonella typhimurium strain. Preincubation with MeIQx demonstrated in mutagenesis experiments that inhibition of Cytochrome P450 (CYP), as well as direct interaction between component(s) of the plant extract with mutagens, might account for the antimutagenic observed effect...

BACKGROUND: The apoptosis of pulmonary artery endothelial cells (PAECs) is an important factor contributing to the development of pulmonary hypertension (PH), a serious cardio-pulmonary vascular disorder. Salidroside (SAL) is a bioactive compound derived from an herb Rhodiola, but the potential protective effects of SAL on PAECs and the underlying mechanisms remain elusive. PURPOSE: The objective of this study was to determine the role of SAL in the hypoxia-induced apoptosis of PAECs and to dissect the underlying mechanisms...

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. This study aimed to investigate the therapeutic effects and mechanism of Jujuboside A on PCOS using a dehydroepiandrosterone (DHEA)-induced PCOS mouse model. Estrogen and androgen homeostasis was evaluated in serum from both clinical samples and PCOS mice. The stages of the estrous cycle were determined based on vaginal cytology. The ovarian morphology was observed by stained with hematoxylin and eosin. Moreover, we analyzed protein expression of cytochrome P450 1A1 (CYP1A1), cytochrome P450 1A2 (CYP1A2) and aryl hydrocarbon receptor (AhR) in ovary and KGN cells...

Colorectal cancer (CRC) is the third leading cause of cancer-related mortalities in the USA and around 52,550 people were expected to die from this disease by December 2023. The objective of this study was to investigate the effect of diet type on benzo(a)pyrene [B(a)P]-induced colon cancer in an adult male rat model, the Polyposis In the Rat Colon (PIRC) kindred type. Groups of PIRC rats (n = 10) were fed with AIN-76A regular diet (RD) or Western diet (WD) and received 25, 50 and 100 µg B(a)P/kg body wt...

Cigarette smoking adversely affects many aspects of human health, and epigenetic responses to smoking may reflect mechanisms that mediate or defend against these effects. Prior studies of smoking and DNA methylation (DNAm), typically measured in leukocytes, have identified numerous smoking-associated regions (e.g., AHRR). To identify smoking-associated DNAm features in typically inaccessible tissues, we generated array-based DNAm data for 916 tissue samples from the GTEx (Genotype-Tissue Expression) project representing 9 tissue types (lung, colon, ovary, prostate, blood, breast, testis, kidney, and muscle)...

OBJECTIVE: Our study aimed to investigate the association between cytochrome P450 1A1 (CYP1A1) polymorphisms (T3801C and A2455G) and acute lymphoblastic leukemia (ALL) risk, considering genetic models and ethnicity. MATERIALS AND METHODS: PubMed, Embase, Web of Knowledge, Scopus, and the Cochrane electronic databases were searched using combinations of keywords related to CYP1A1 polymorphisms and the risk of ALL. Studies retrieved from the database searches underwent screening based on strict inclusion and exclusion criteria...

The human lymphoblastoid cell line TK6 stands out as the most widely employed human cell line in genotoxicity testing, as recommended by various testing guidelines for in vitro assessments. Nevertheless, like many testing cell lines, TK6 lacks functional phase I drug-metabolizing enzymes crucial for chemical genotoxicity evaluations. This protocol introduces a lentivirus-based methodology for establishing a panel of TK6-derived cell lines, each expressing one of 14 cytochrome P450s (CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, and CYP3A7)...

OBJECTIVES: The principal motive of this study is to explore the influence maternal separation (MS) exhibits on the mRNA expression of major drug metabolizing-cyp450s in parallel with the assessment of pathological changes that can be induced by MS in the livers of experimental mice. METHODS: Eighteen Balb/c mouse pups, comprising of both males and females, were separated from their mothers after birth. Following a six-week period during when the pups became adults, the mice were sacrificed and their livers were isolated for analysis of weight, pathohistological alterations, and the mRNA expression of drug metabolizing cyp450 genes: cyp1a1 , cyp3a11 , cyp2d9 , and cyp2c29 ...

Urban Particulate Matter (UPM) induces skin aging and inflammatory responses by regulating skin cells through the transient receptor potential vanilloid 1 (TRPV1). Although oleic acid, an unsaturated free fatty acid (FFA), has some functional activities, its effect on UPM-induced skin damage has not been elucidated. Here, we investigated signaling pathways on how oleic acid is involved in attenuating UPM induced cell damage. UPM treatment increased XRE-promoter luciferase activity and increased translocation of AhR to the nucleus, resulting in the upregulation of CYP1A1 gene...