CYP1A1

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...

Chronic kidney disease (CKD) is the 16th leading cause of mortality worldwide. Clinical studies have raised that long-term use of omeprazole (OME) is associated with the morbidity of CKD. OME is commonly used in clinical practice to treat peptic ulcers and gastroesophageal reflux disease. However, the mechanism underlying renal failure following OME treatment remains mostly unknown and the rodent model of OME-induced CKD is yet to be established. We described the process of renal injury after exposure to OME in mice; the early renal injury markers were increased in renal tubular epithelial cells (RTECs)...

Smoking is a risk factor for non-small cell lung cancer (NSCLC). The most common subtypes of NSCLC are lung adenocarcinoma (LAC) and squamous cell carcinoma (SCC). The cigarette smoke contains aryl hydrocarbon receptor (AhR) ligands, such as benzo(a)pyrene (BaP). By activating the AhR, BaP can change the expression of many genes, including miRNA-encoding genes. In this study, we have evaluated the expression of few miRNAs potentially regulated by AhR (miR-21, -342, -93, -181a, -146a), as well as CYP1A1, a known AhR target gene, in lung tumor samples from smoking (n=40) and non-smoking (n=30) patients with LAC and from smoking patients with SCC (n=40)...

Background: Publications on the associations of genetic variants with the response to platinum-based chemotherapy (PBC) in NSCLC patients have surged over the years, but the results have been inconsistent. Here, a comprehensive meta-analysis was conducted to combine eligible studies for a more accurate assessment of the pharmacogenetics of PBC in NSCLC patients. Methods: Relevant publications were searched in PubMed, Scopus, and Web of Science databases through 15 May 2021. Inclusion criteria for eligible publications include studies that reported genotype and allele frequencies of NSCLC patients treated with PBC, delineated by their treatment response (sensitive vs...

Gut microbiota regulates various aspects of human physiology by producing metabolites, metabolizing enzymes, and toxins. Many studies have linked microbiota with human health and altered microbiome configurations with the occurrence of several diseases, including cancer. Accumulating evidence suggests that the microbiome can influence the initiation and progression of several cancers. Moreover, some microbiotas of the gut and oral cavity have been reported to infect tumors, initiate metastasis, and promote the spread of cancer to distant organs, thereby influencing the clinical outcome of cancer patients...

To determine the efficacy and potential protective mechanism of canagliflozin combined with aerobic exercise in treating chronic heart failure (CHF). Isoproterenol was injected into rats to create CHF models. The rats were then subsequently divided into saline, canagliflozin (3 mg/kg/d), aerobic exercise training, and canagliflozin combined with aerobic exercise training. Compared to the CHF group, the canagliflozin combined with the aerobic exercise group had superior ventricular remodeling and cardiac function...

As the largest organ, the skin provides the first line of defence against environmental pollutants. Different pollutants have varied damage to the skin due to their own physical-chemical properties. A previous epidemiological study by our team revealed that eczema was positively correlated with different air pollutants. However, the mechanism of action from different pollutants on the skin is less known. In this work, the differences among the genotoxicity, intracellular reactive oxygen species, and barrier-related parameters caused by two kinds of air pollutants, that is, S1650b and carbon black (CB) were investigated by Western blot, TUNEL, comet assay and RNA-sequences...

Smoking is a potent cause of asthma exacerbations, chronic obstructive pulmonary disease (COPD) and many other health defects, and changes in DNA methylation (DNAm) have been identified as a potential link between smoking and these health outcomes. However, most studies of smoking and DNAm have been done using blood and other easily accessible tissues in humans, while evidence from more directly affected tissues such as the lungs is lacking. Here, we identified DNAm patterns in the lungs that are altered by smoking...

Dimethylmonothioarsinic acid (DMMTAV ), a pentavalent thio-arsenic derivative, has been found in bodily fluids and tissues including urine, liver, kidney homogenates, plasma, and red blood cells. Although DMMTAV is a minor metabolite in humans and animals, its substantial toxicity raises concerns about potential carcinogenic effects. This toxicity could be attributed to arsenicals' ability to regulate cytochrome P450 1A (CYP1A) enzymes, pivotal in procarcinogen activation or detoxification. The current study investigates DMMTAV 's impact on CYP1A1/2 expression, individually and in conjunction with its inducer, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)...

Breast cancer is one of the main causes of malignancy-related deaths globally and has a significant impact on women's quality of life. Despite significant therapeutic advances, there is a medical need targeted therapies in breast cancer. Aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor mediates responses to environment stimuli, is emerging as a unique pleiotropic target. Herein, a combined molecular simulation and in vitro investigations identified 3-(3-fluorophenyl)-1H-pyrazolo[3,4-b]pyridine (3FPP) as a novel AhR ligand in T47D and MDA-MB-231 breast cancer cells...

Obesity, a key contributor to metabolic disorders, necessitates an in-depth understanding of its pathogenesis and prerequisites for prevention. Guangxi Bama miniature pig (GBM) offers an apt model for obesity-related studies. In this research, we used transcriptomics and 16S rRNA gene sequencing to discern the differentially expressed genes (DEGs) within intestinal (jejunum, ileum, and colon) tissues and variations in microbial communities in intestinal contents of GBM subjected to normal diets (ND) and high-fat, high-carbohydrate diets (HFHCD)...

Ochratoxin A (OTA), a common mycotoxin, can contaminate food and feed and is difficult to remove. Astaxanthin (ASTA), a natural antioxidant, can effectively protect against OTA-induced hepatotoxicity; however, its mechanism of action remains unclear. In the present study, we elucidate the protective effects of ASTA on the OTA-induced damage of the endoplasmic reticulum and mitochondria in broiler liver samples by serum biochemical analysis, antioxidant analysis, qRT-PCR, and Western blot analysis. ASTA inhibited the expressions of ahr , pxr , car , cyp1a1 , cyp1a5 , cyp2c18 , cyp2d6 , and cyp3a9 genes, and significantly alleviated OTA-induced liver oxidative damage (SOD, GSH-Px, GSH, MDA)...

Aflatoxin B1 (AFB1) is the most toxic mycotoxin and a proven human carcinogen that requires metabolic activation, known by cytochrome P450 (CYP) 1A2 and 3A4. Previous evidence showed that AFB1 is activated by human recombinant CYP1A1 expressed in budding yeast. Yet, the toxicity, in particular the genotoxicity of the reactive metabolites formed from AFB1 remains unclear. Humans could be exposed to both AFB1 and benzo(a)pyrene (BaP) simultaneously, thus we were interested in their combined genotoxic effects subsequent to metabolic activation by CYP1A1...

BACKGROUND: Last few decades, multiple studies all over the world revealed the association of genetic polymorphism in cytochrome P450 (CYP) genes with risk of developing different type of cancers, but contradictory outcomes were evidenced in case of cervical cancer (CC) risk. Therefore, the discrepancies in earlier reports influenced us to evaluate the association of CYP1A1*2A rs4646903, CYP1B1*3 rs1056836, CYP2C8*2 rs11572103, CYP2C9*2 rs1799853, CYP2C9*3 rs1057910, and CYP2C19*2 rs4244285 polymorphisms and CC susceptibility in the women of rural population of Maharashtra...

Dioxin-like pollutants (DLPs), such as polychlorinated biphenyl 126 (PCB 126), are synthetic chemicals classified as persistent organic pollutants. They accumulate in adipose tissue and have been linked to cardiometabolic disorders, including fatty liver disease. The toxicity of these compounds is associated with activation of the aryl hydrocarbon receptor (Ahr), leading to the induction of phase I metabolizing enzyme cytochrome P4501a1 (Cyp1a1) and the subsequent production of reactive oxygen species (ROS)...

Histone modifications maintain genomic stability and orchestrate gene expression at the chromatin level. Benzo [a]pyrene (BaP) is the ubiquitous carcinogen widely spread in the environment, but the role and regulatory mechanism of histone modification in its toxic effects remain largely undefined. In this study, we found a dose-dependent reduction of histone H3 methylations at lysine4, lysine9, lysine27, lysine36 in HBE cells treated with BaP. We observed that inhibiting H3K27 and H3K36 methylation impaired cell proliferation, whereas the loss of H3K4, H3K9, H3K27, and H3K36 methylation led to increased genomic instability and delayed DNA repair...