Ask about this productRelated genes to: CYP1A2 antibody
- Gene:
- CYP1A2 NIH gene
- Name:
- cytochrome P450 family 1 subfamily A member 2
- Previous symbol:
- -
- Synonyms:
- P3-450, CP12
- Chromosome:
- 15q24.1
- Locus Type:
- gene with protein product
- Date approved:
- 1990-04-25
- Date modifiied:
- 2019-04-23
Related products to: CYP1A2 antibody
Related articles to: CYP1A2 antibody
- Cytochrome P450 (CYP)-mediated biotransformation of endogenous and xenobiotic substances can lead to altered exposure, toxicological impact, or adverse drug reactions. CYP induction data are fundamental to regulatory chemical hazard assessment because they directly affect the in vivo fate of xenobiotics, potentially influencing the safety and efficacy of pharmaceuticals, and impacting the safety assessment of industrial chemicals and environmental contaminants. Here we report the results on part 2 of the supplementary validation study of an established and previously validated in vitro method using human HepaRGTM cells able to detect CYP1A2, CYP2B6 and CYP3A4 induction to support the expansion of the method's chemical applicability domain beyond pharmaceuticals. This study addresses needs arising from part 1 of the study. We established the test method using ten previously validated pharmaceutical proficiency chemicals, then tested a further six proposed augmentation chemicals, tebuconazole, benfuracarb, chlorpyrifos, N, N-diethyl-meta-toluamide, fipronil, and permethrin (supporting part 1), and then four additional chemicals, prochloraz, atrazine, pyrimethanil and chlorpyrifos-methyl. LC-MS/MS was utilized to measure the conversion of a cocktail mixture of prototypical selective CYP probe substrates to their metabolites, in parallel with mRNA measurements. We achieved high concordance with predicted activity for the proficiency and augmentation chemicals for CYP1A2 and CYP3A4, though with greater uncertainty for CYP2B6. Together with the part 1 study, these data were sufficient to support acceptance of the HepaRG™ method for CYP induction testing and its adoption as OECD TG 445A. Tentative comparisons with mRNA based measurements suggested gene expression may serve as a complementary but not validated tool. - Source: PubMed
Publication date: 2026/09/25
Quartermain EmmaZhang JinkangMarczylo TimGant Timothy WJacobs Miriam N - In this article, the three-dimensional (3D) adipose-derived stem cells (ADSCs) differentiated into hepatocyte-like cells were fabricated on polycaprolactone (PCL)/sodium alginate/gelatin hydrogel scaffolds. To this end, the 3D scaffold was fabricated applying PCL, sodium alginate, and gelatin hydrogel using electrospinning machine. During the fabrication and testing of scaffold, the human ADSCs were transformed into hepatocyte cells using the mesenchymal process for 21 days. Human placenta extract (HPE) was used in the cell culture to increase cell growth, proliferation, and differentiation. The results indicated the tensile elastic modulus of the scaffold at 85.5 ± 15.5 kPa. The contact angle and porosity values were 67.7° and 71.351%, respectively. The swelling and degradation percentages were 22.308%, 1.778% (1 h), 53.385%, 5.111% (24 h), and finally 71.318% and 17.778% (14 days). Based on the dynamic light scattering image, the diameter size of the HPE and alginate nanoparticles was between 10 and 100 nm. According to the cell viability analysis for 72 h, the optimized HPE value was 0.64%. Based on the results of the oil-red O staining and alizarin red staining, ∼80% of the ADSCs differentiated successfully into adipogenic and osteogenically formats. The orders of different formats of ADSCs for cell proliferations, resistance to cisplatin drug experiments, fold change factor for PXR, CYP1A2, and albumin gene concentration were 3D ADSC plus HPE, 2D ADSC plus HPE, 3D ADSC, and ADSC models as the first to fourth, respectively. Due to flow cytometry test, surface markers CD31 and CD45 were negative, whereas CD90 and CD105 were positive. - Source: PubMed
Publication date: 2026/09/28
Mahin Shafie FarimahSadeghi AliShojaei ShahrokhLafouti Mansoureh - Global anthropogenic climate change is restructuring the thermohygric parameters that govern Aspergillus flavus and Aspergillus parasiticus ecology, expanding the geographic range and contamination intensity of aflatoxin in staple food crops worldwide. Aflatoxin B1, a Group 1 IARC carcinogen and the most potent naturally occurring hepatocarcinogen, undergoes CYP3A4/CYP1A2-mediated bioactivation to the exo-8,9-epoxide, which alkylates N7-guanine residues in DNA, generating AFB1-N7-guanine adducts that produce G → T transversions culminating in the TP53 R249S gain-of-function mutation, a molecular fingerprint of aflatoxin-driven hepatocellular carcinoma. Beyond direct genotoxicity, AFB1 drives mitochondrial dysfunction through oxidative phosphorylation impairment, glutathione depletion, cardiolipin peroxidation, and mitochondrial membrane potential collapse. It activates NF-κB, STAT3, and TGF-β inflammatory signaling; and engages hepatic stellate cells in fibrogenesis culminating in cirrhosis. Critically, AFB1 also disrupts the gut microbiome, depleting butyrateproducing Ruminococcaceae, Faecalibacterium prausnitzii, and Akkermansia muciniphila while expanding pro-inflammatory Proteobacteria and Enterobacteriaceae. These dysbiotic changes compromise tight junction integrity, increase intestinal permeability, elevate portal LPS, and activate hepatic TLR4/MyD88/NF-κB and NLRP3 inflammasome cascades that amplify the carcinogenic consequences of direct AFB1 genotoxicity. This review integrates mechanistic evidence from molecular toxicology, microbiome biology, immunometabolism, and systems oncology to establish a unified framework positioning gut dysbiosis as a modifiable intermediate pathway in climate-sensitive aflatoxin-driven carcinogenesis. - Source: PubMed
Publication date: 2026/09/28
Oyedokun Precious AdeoyeOwolabi Victor PelumiOyedokun Marvelous DasolaNdako James AjigasokoaAdegbola Peter IfeoluwaOyedokun Nicodemus Adeyemi - The surge in the consumption of commercial herbal supplement juice (CHSJ) is driven by the perception that natural products are inherently safe. However, many reach the market without rigorous toxicological evaluation, posing a hidden risk to public health. Despite their popularity, data regarding the hepatotoxic profiles of CHSJ and their interference with drug-metabolizing enzymes remain scarce. The present study addresses this critical knowledge gap by providing a multi-analytical toxicological characterization in vitro of a commercially available CHSJ, namely, Sample A marketed for women's reproductive health in Malaysia. This study evaluated the hepatotoxicity and cytochrome P450 (CYP) inhibitory potential of Sample A, using the in vitro HepG2 cell model. The phytochemical profile of Sample A was characterized via liquid chromatography-mass spectrometry (LC-MS). Cytotoxicity was assessed through the MTT assay, whereas oxidative stress was measured using the DCFH-DA ROS assay. Hepatotoxic effects were evaluated through alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity assays and H&E staining for morphological changes. Furthermore, the modulation of CYP1A2, CYP2C9, CYP2D6, and CYP3A4 was investigated at both the transcriptional level (RT-qPCR) and through functional activity using recombinant human CYP enzymes. Sample A exerts a concentration- and time-dependent cytotoxic effect on HepG2 cells, associated with uncompensated intracellular oxidative stress beginning at 2% v/v concentration. This early adaptive stress was biochemically characterized by elevated intracellular AST (1% v/v) and ALT (5% v/v) activities. This was then structurally validated by H&E staining showing prominent histopathological alterations in the treated HepG2 cells. Simultaneously, Sample A acts as potent, multitarget modulator of Phase I xenobiotic metabolism. It near-completely inhibited functional CYP3A4 activity at concentrations as low as 0.50% v/v, while reducing the transcriptional mRNA expression of CYP1A2 and CYP2C9 at 0.75% v/v. The findings demonstrate that this commercial formulation poses a dual threat of hepatotoxicity and xenobiotic metabolic interference. Sample A poses a risk of herb-induced liver injury and potentially significant herb-drug interactions. These insights underscore an urgent need for stricter regulatory oversight, standardized premarket evaluation, and enhanced public safety awareness regarding uncharacterized commercial polyherbal formulations. - Source: PubMed
Publication date: 2026/09/27
Lim Yih WeiHadi Alya Fakhira HasnulSarchio Seri Narti EdayuZulkafli Intan SuhanaShamsi Suhaili - California's Proposition 65 requires warning labels for chemicals associated with carcinogenicity or reproductive toxicity, affecting global cosmetic and fragrance formulations. While safrole has an established safe harbor level (No Significant Risk Level, NSRL) of 3 µg/day, its structural analogues, estragole and methyleugenol, lack specific safe harbor thresholds. To address this data gap using non-animal methodologies, this study evaluated a Next-Generation Risk Assessment (NGRA) workflow combining read-across and modeling. Structural, physicochemical, and skin-permeation profiling supported category homogeneity (Tanimoto ≥ 0.82 and comparable log values) in accordance with OECD and ECHA guidelines. Multi-platform QSAR consensus (ToxTree, Danish QSAR, and VEGA QSAR) indicated that while parent phenylpropenes lack direct bacterial mutagenicity, they share a hepatic bioactivation pathway leading to mammalian clastogenicity and carcinogenicity predictions. Molecular docking with human Cytochrome P450 1A2 (CYP1A2; PDB: 2H14) identified safrole as the category's conservative toxicological benchmark, exhibiting the highest binding affinity (-8.026 kcal/mol) and closest proximity to the catalytic HEME iron. Consequently, applying safrole's 3 µg/day NSRL to estragole and methyleugenol provides a quantitative threshold to evaluate consumer exposure in cosmetic products, ensuring public health protection and regulatory compliance. - Source: PubMed
Publication date: 2026/09/04
Corrêa Gabriela de Oliveira PradoSouza TugstênioConde Eduarda Naomi NakanoOliveira Andréia Ávila SoaresVita Natália AlbuquerqueMotter Catarino CarolinaCanavez Andrezza di Pietro Micali