The CYP1A1 Knockout THP-1 Cell Line is a Homo sapiens-derived cellular model featuring CRISPR/Cas9-mediated disruption of the CYP1A1 gene in the well-established THP-1 human acute monocytic leukemia cell line. This knockout cell line serves as a loss-of-function tool for investigating the roles of cytochrome P450 family 1 subfamily A member 1 (CYP1A1) in xenobiotic metabolism, chemical carcinogenesis, and immune cell biology. The gene-edited cells offer a stable and heritable ablation of CYP1A1 expression, enabling precise dissection of the enzyme??s contribution to the bioactivation and detoxification of polycyclic aromatic hydrocarbons (PAHs) and other environmental procarcinogens. As a cell-line format product, it is suitable for in vitro applications that require consistent and reproducible CYP1A1-deficient monocyte/macrophage models.
The THP-1 parental cell line originates from the peripheral blood of a one-year-old male patient with acute monocytic leukemia and is widely utilized as a model for monocyte-to-macrophage differentiation and inflammatory signaling. THP-1 cells grow as a non-adherent suspension culture and can be induced to differentiate into adherent, macrophage-like cells upon stimulation with phorbol 12-myristate 13-acetate (PMA), thereby recapitulating key features of tissue-resident macrophages. This differentiation capability makes the CYP1A1 Knockout THP-1 Cell Line particularly valuable for examining gene?Cenvironment interactions within the innate immune system, especially in the context of aryl hydrocarbon receptor (AhR)-dependent pathways.
CYP1A1 encodes a phase I xenobiotic-metabolizing enzyme that functions primarily as an aryl hydrocarbon hydroxylase, catalyzing the monooxygenation of PAHs such as benzo[a]pyrene to generate reactive epoxide intermediates. Transcription of CYP1A1 is tightly controlled by the AhR signaling cascade: upon binding ligands like ??-naphthoflavone, dioxins, or PAHs, AhR translocates to the nucleus in complex with ARNT and binds xenobiotic response elements (XREs) to induce CYP1A1 expression. The enzyme requires physical interaction with NADPH?Ccytochrome P450 reductase (POR) for its catalytic activity, and its metabolic products include BPDE?CDNA adducts, reactive oxygen species (ROS), and activated procarcinogens that promote mutagenesis and oxidative stress. Additionally, CYP1A1 can hydroxylate 17??-estradiol, linking it to hormone-related carcinogenesis. By disrupting CYP1A1, this knockout cell line eliminates the primary enzymatic conduit for AhR-dependent metabolic activation of environmental toxicants.
In macrophages, CYP1A1 is induced by AhR agonists and contributes to the metabolic processing of inhaled and circulating xenobiotics, influencing both pro-inflammatory signaling and genotoxic risk. The CYP1A1 Knockout THP-1 Cell Line enables researchers to separate the direct AhR transcriptional program from the metabolic feedback generated by CYP1A1 activity, yielding clearer insights into immunomodulatory effects of PAHs and dioxins. Because THP-1-derived macrophages are phagocytic and secrete a wide range of cytokines, this knockout model is particularly suited for evaluating how CYP1A1-mediated metabolism alters macrophage phenotype, inflammasome activation, and the balance between detoxification and bioactivation in the tumor microenvironment or in chronic inflammatory diseases such as chronic obstructive pulmonary disease.
Typical applications include studying CYP1A1-dependent bioactivation of procarcinogens in macrophage lineage cells using EROD activity assays and LC-MS/MS-based quantification of DNA adducts, as well as profiling AhR pathway activation through luciferase reporter assays. The knockout cell line facilitates dissection of ROS-mediated genotoxicity and apoptosis following exposure to cigarette smoke condensate or individual PAHs, combined with RT-qPCR and Western blot analyses of CYP1A1 downstream effectors. Furthermore, it provides a clean background for screening AhR agonists and antagonists, and for assessing how CYP1A1 deficiency alters phagocytosis and cytokine secretion in PMA-differentiated macrophages challenged with environmental pollutants. For further technical details, including validation data and batch-specific quality metrics, please contact Ascent Research.
