Discrimination of Tumorigenic Triazole Conazoles from Phenobarbital by Transcriptional Analyses of Mouse Liver Gene Expression
TOXICOLOGICAL SCIENCES
Authors: Nesnow, Stephen; Ward, William; Moore, Tanya; Ren, Hongzu; Hester, Susan D.
Abstract
Conazoles are fungicides used to control fungal growth in environmental settings and to treat humans with fungal infections. Mouse hepatotumorigenic conazoles display many of the same hepatic toxicologic responses as the mouse liver carcinogen phenobarbital (PB): constitutive androstane receptor (CAR) activation, hypertrophy, Cyp2b induction, and increased cell proliferation. The goal of this study was to apply transcriptional analyses to hepatic tissues from mice exposed to PB, propiconazole (Pro) or triadimefon (Tri) at tumorigenic exposure levels to reveal similarities and differences in response among these treatments. Mice were administered diets containing PB (850 ppm), Pro (2500 ppm), or Tri (1800 ppm) for 4 and 30 days. Targeted transcriptomic analyses were conducted at the gene level examining differentially expressed genes (DEGs), and subsets of DEGs: cell cycle genes, and transcription factors. Analyses were also conducted on function, pathway and network levels examining Ingenuity Pathway Analysis Tox Lists and Canonical Pathways, and Gene-Go MetaCore dynamic networks and their central hubs. Genes expressed by PB or the two conazoles were also compared with those genes associated with human hepatocellular cancer. The results from these analyses indicated greater differences between PB and the two conazoles than similarities. Significant commonalities between the two conazole treatments were also noted. We posit that the transcriptional profiles of tissues exposed to toxic chemicals inherently contain their mechanisms of toxicity. We conclude that although PB and these 2 conazoles induce mouse liver tumors and exhibit similar toxicological responses, their transcriptional profiles are significantly different and thus their mechanisms of tumorigenic action are likely to differ.
A Novel CdSe/ZnS Quantum Dots Fluorescence Assay Based on Molecularly Imprinted Sensitive Membranes for Determination of Triazophos Residues in Cabbage and Apple
FRONTIERS IN CHEMISTRY
Authors: Hong, Sihui; She, Yongxin; Cao, Xiaolin; Wang, Miao; He, Yahui; Zheng, Lufei; Wang, Shanshan; Abd El-Aty, A. M.; Hacimuftuoglu, Ahmet; Yan, Mengmeng; Wang, Jing
Abstract
In the present study we have developed a direct competitive CdSe/ZnS quantumdot (QD) fluorescence assay based on micro-array-imprinted membranes for the determination of triazophos in cabbage and apple. The imprinted membranes were directly synthesized on the surface of a 96-well plate by thermal polymerization using triadimefon as the dummy template. Under optimal conditions, the assay showed an excellent linear response over the concentration ranges of 0.1-10,000 mu g L-1 with a good coefficient of determination (R-2= 0.982). The sensitivity (IC50) and limit of detection (LOD, expressed as IC15) of the developed assay were 3.63 mg L-1 and 0.31 mu g L-1, respectively. The applicability of the developed approach was tested for detecting triazophos in incurred samples. Themethod showed excellent recoveries (109.6-118.9%) and relative standard deviations (RSDs) between 9.9 and 19.5%. The obtained results correlated well with those obtained by LC-MS/MS (R-2= 0.9995). The competitive assay using CdSe/ZnS QDs as fluorescence-labeled probe showed good sensitivity, steady and fast response, and excellent anti-interference ability compared to conventional fluorescence-quenching methods. Finally, the feasibility of the proposed methodology was successfully applied for detection of triazophos in real samples.