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        <title>Frontiers in Genetics | Predictive Toxicology and Exposomics section | New and Recent Articles</title>
        <link>https://www.frontiersin.org/journals/genetics/sections/predictive-toxicology-and-exposomics</link>
        <description>RSS Feed for Predictive Toxicology and Exposomics section in the Frontiers in Genetics journal | New and Recent Articles</description>
        <language>en-us</language>
        <generator>Frontiers Feed Generator,version:1</generator>
        <pubDate>2026-05-12T20:07:11.333+00:00</pubDate>
        <ttl>60</ttl>
        <item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fgene.2026.1807152</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fgene.2026.1807152</link>
        <title><![CDATA[Perfluorooctanesulfonic acid contributes to primary open-angle glaucoma in a FABP4-Dependent manner: a novel mechanism for environmental risk of glaucoma]]></title>
        <pubdate>2026-05-12T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Jiangpeng Lin</author><author>Yichi Zhang</author><author>Yunzepeng Li</author><author>Nan He</author><author>Yang Liu</author><author>Hui Zheng</author>
        <description><![CDATA[BackgroundPrimary open-angle glaucoma (POAG) is the most prevalent form of glaucoma globally, with environmental factors increasingly recognized as critical determinants of its onset and progression. However, the potential association between perfluorooctanesulfonic acid (PFOS) exposure and POAG remains poorly understood, and its underlying molecular mechanisms have yet to be elucidated.Methods and resultsUtilizing cross-sectional data from the NHANES database, we identified a significant positive correlation between serum PFOS levels and glaucoma prevalence. The robustness of our study population selection and the focus on POAG were further validated through the Global Burden of Disease (GBD) database and systematic literature review. Network toxicology analysis identified 20 PFOS-exposure-related genes in POAG, with functional enrichment highlighting the biosynthesis of unsaturated fatty acids as a key pathway. Integrated machine learning and bioinformatic analysis pinpointed FABP4 as a pivotal candidate gene. Molecular docking and dynamics simulations confirmed stable binding affinity between PFOS and the FABP4 protein. In vitro experiments using human trabecular meshwork cells (HTMCs) demonstrated that PFOS exposure induced cellular senescence, as evidenced by SA-β-gal staining. Western blot analysis revealed that PFOS significantly upregulated the expression of FABP4 and the senescence marker P21. Crucially, targeted functional inhibition of the FABP4 protein successfully rescued PFOS-induced senescence and downregulated P21 expression.ConclusionThese findings provide novel insights into the toxicological profile of PFOS, suggesting that it contributes to POAG pathogenesis by modulating FABP4-mediated cellular senescence. This study offers a theoretical basis for environmental risk assessment and the development of preventive strategies for POAG.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fgene.2025.1672729</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fgene.2025.1672729</link>
        <title><![CDATA[Non-polar components in PM2.5 increase matrix remodeling of CRS by up-regulating CEMIP in nasal fibroblasts]]></title>
        <pubdate>2025-10-23T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Jiayao Zhou</author><author>Ying Zhu</author><author>Huilin Hu</author><author>Ru Tang</author><author>Shiyao Zhang</author><author>Yuelong Gu</author><author>Song Mao</author><author>Shilei Pu</author><author>Hai Lin</author><author>Yue Zhao</author><author>Zhipeng Li</author><author>Weitian Zhang</author>
        <description><![CDATA[BackgroundFine particulate matter (PM2.5) is harmful to respiratory health and can lead to chronic rhinosinusitis (CRS). But how its components lead to CRS by affecting the function of nasal fibroblasts remains unclear.MethodsIn this study, polar organic components (P-OC) and non-polar organic components (N-OC) isolated from PM2.5 were used to intervene human nasal fibroblasts (hNFs), respectively. CCK8 assay and LDH assay were used to detect cell viability, and scratch assay was used to detect cell migration ability. Gene expression changes were detected by RNA-sequencing and molecular biology.ResultsP-OC inhibited the viability and migration of hNFs, while N-OC significantly promoted the migration of hNFs. The expression of CEMIP, MMP1 and IL-1β was upregulated after N-OC treatment. CEMIP gene silencing inhibited hNFs migration and the expression of MMP1 and IL-1β. The effect of PAHs exposure on cells was more obvious than n-alkanes.ConclusionN-OC in PM2.5, especially PAHs, can aggravate CRS by activating hNFs through CEMIP. This study provides new ideas for exploring the pathogenic mechanism of air pollution on upper respiratory diseases.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fgene.2025.1608524</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fgene.2025.1608524</link>
        <title><![CDATA[Editorial: Impact of heavy metal on aquatic life and human health]]></title>
        <pubdate>2025-04-23T00:00:00Z</pubdate>
        <category>Editorial</category>
        <author>Ahmed H. El-Sappah</author><author>Heba H. Abdel-Kader</author><author>Manzar Abbas</author><author>Sara Zafar</author><author>Jia Li</author>
        <description></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fgene.2025.1479307</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fgene.2025.1479307</link>
        <title><![CDATA[Checkpoint and recombination pathways independently suppress rates of spontaneous homology-directed chromosomal translocations in budding yeast]]></title>
        <pubdate>2025-04-04T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Li Zeng</author><author>Mingzeng Sun</author><author>Michael Fasullo</author>
        <description><![CDATA[Homologous recombination between short repeated sequences, such as Alu sequences, can generate pathogenic chromosomal rearrangements. We used budding yeast to measure homologous recombination between short repeated his3 sequences located on non-homologous chromosomes to identify pathways that suppress spontaneous and radiation-associated translocations. Previous published data demonstrated that genes that participate in RAD9-mediated G2 arrest, the S phase checkpoint, and recombinational repair of double-strand breaks (DSBs) suppressed ectopic recombination between small repeats. We determined whether these pathways are independent in suppressing recombination by measuring frequencies of spontaneous recombination in single and double mutants. In the wild-type diploid, the rate of spontaneous recombination was (3 ± 1.2) × 10−8. This rate was increased 10–30-fold in the rad51, rad55, rad57, mre11, rad50, and xrs2 mutants, seven-fold in the rad9 checkpoint mutant, and 23-fold in the mec1-21 S phase checkpoint mutant. Double mutants defective in both RAD9 and in either RAD51, RAD55, or RAD57 increased spontaneous recombination rates by ∼40 fold, while double mutants defective in both the MEC1 (ATR/ATM ortholog) and RAD51 genes increased rates ∼100 fold. Compared to frequencies of radiation-associated translocations in wild type, radiation-associated frequencies increased in mre11, rad50, xrs2, rad51, rad55 and rad9 rad51 diploid mutants; an increase in radiation-associated frequencies was detected in the rad9 rad51 diploid after exposure to 100 rads X rays. These data indicate that the S phase and G2 checkpoint pathways are independent from the recombinational repair pathway in suppressing homology-directed translocations in yeast.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fgene.2025.1505379</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fgene.2025.1505379</link>
        <title><![CDATA[Differentially expressed and alternately spliced genes as a novel tool for genotoxicity: a computerized study in ATT-myc transgenic mice for the recognition of genotoxic and non-genotoxic chemical]]></title>
        <pubdate>2025-03-28T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Mansour A. Alghamdi</author><author>Eman M. El Nashar</author><author>Mahmoud Elalfy</author><author>Norah S. Al-Zahrani</author><author>Mohammed A. Alshehri</author><author>Mohammad El-Nablaway</author><author>Khulood M. Al-Khater</author><author>Rashid A. Aldahhan</author><author>Eman G. El-Hadidy</author><author>Fathy Sleem</author><author>Ahmed Aljazzar</author><author>Jürgen Borlak</author><author>Mona Elhadidy</author>
        <description><![CDATA[BackgroundTransgenic mice and gene expression in analyses were employed to evaluate hazardous chemicals.MethodsMice received weekly doses of NDEA (75 mg/kg) for six weeks and twice-weekly doses of BHT (300 mg/kg) for eight weeks. Gene expression and splicing alterations in the livers of six transgenic mice for each treatment of NDEA and BHT were examined using the MouseExon10ST array.ResultsSix hybridizations revealed 645 genes with significant expression changes, and 181 genes showed both expression and splicing alterations (p < 0.01). Furthermore, 2021 genes demonstrated significant exon–group interactions, indicating potential alternative splicing. Pathway analysis identified enriched groups in GOMolFn, GOProcess, GOCellLoc, and Pathway classes, with a higher representation of alternatively spliced and expressed genes (p < 0.01).DiscussionAmong the top expressed genes was TAT, which encodes the mitochondrial enzyme tyrosine aminotransferase, involved in tyrosine metabolism and recognized as a novel tumor suppressor gene linked to hepatocellular carcinoma (HCC). Additionally, HNF-4, a transcription factor, plays a crucial role in TAT expression.ConclusionsThis method can be used to identify genotoxic compounds in the att-myc model for short-term toxicity.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fgene.2025.1524433</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fgene.2025.1524433</link>
        <title><![CDATA[Blood toxicogenomics reveals potential biomarkers for management of idiosyncratic drug-induced liver injury]]></title>
        <pubdate>2025-03-25T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Rachel J. Church</author><author>Benedict Anchang</author><author>Brian D. Bennett</author><author>Pierre R. Bushel</author><author>Paul B. Watkins</author>
        <description><![CDATA[Introduction: Accurate diagnosis, assessment, and prognosis of idiosyncratic drug-induced liver injury (IDILI) is problematic, in part due to the shortcomings of traditional blood biomarkers. Studies in rodents and healthy volunteers have supported that RNA transcript changes in whole blood may address some of these shortcomings.Methods: In this study, we conducted RNA-Seq analysis on peripheral blood samples collected from 55 patients with acute IDILI and 17 patients with liver injuries not attributed to IDILI.Results and discussion: Three differentially expressed genes (DEGs; CFD, SQLE, and INKA1) were identified as significantly associated with IDILI vs. other liver injuries. No DEGs were identified comparing IDILI patients to the 5 patients with autoimmune hepatitis, suggesting possible common underlying mechanisms. Two genes (VMO1 and EFNA1) were significantly associated with hepatocellular injury compared to mixed/cholestatic injury. When patients with severe vs. milder IDILI were compared, we identified over 500 DEGs. The top pathways identified from these DEGs had in common down regulation of multiple T-cell specific genes. Further analyses confirmed that these changes could largely be accounted for by a fall in the concentration of circulating T-cells during severe DILI, perhaps due to exhaustion or sequestration of these cells in the liver. Exploration of DEGs specific for the individual causal agents was largely unsuccessful, but isoniazid-induced IDILI demonstrated 25 DEGs compared to other non-isoniazid IDILI cases. Finally, among the 14 IDILI patients that had hepatocellular jaundice (i.e., Hy’s Law cases), we identified 39 DEGs between the 4 patients with fatal or liver transplantation outcomes compared to those that recovered. These findings suggest the potential for blood-based transcriptomic biomarkers to aid in the diagnosis and prognostic stratification of IDILI.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fgene.2025.1538168</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fgene.2025.1538168</link>
        <title><![CDATA[Tetrahymena thermophila glutathione-S-transferase superfamily: an eco-paralogs gene network differentially responding to various environmental abiotic stressors and an update on this gene family in ciliates]]></title>
        <pubdate>2025-03-07T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Ruth Ortega</author><author>Ana Martin-González</author><author>Juan-Carlos Gutiérrez</author>
        <description><![CDATA[Glutathione S-transferases constitute a superfamily of enzymes involved mainly, but not exclusively, in the detoxification of xenobiotic compounds that are considered environmental pollutants. In this work, an updated analysis of putative cytosolic glutathione S-transferases (cGST) from ciliate protozoa is performed although this analysis is mainly focused on Tetrahymena thermophila. Among ciliates, the genus Tetrahymena has the highest number (58 on average) of cGST genes. As in mammals, the Mu class of cGST is present in all analyzed ciliates and is the majority class in Tetrahymena species. After an analysis of the occurrence of GST domains in T. thermophila, out of the 54 GSTs previously considered to be Mu class, six of them have been discarded as they do not have recognizable GST domains. In addition, there is one GST species-specific and another GST-EF1G (elongation factor 1 gamma). A structural analysis of T. thermophila GSTs has shown a wide variety of β-sheets/α-helix patterns, one of the most abundant being the canonical thioredoxin-folding pattern. Within the categories of bZIP and C4 zinc finger transcription factors, potential binding sites for c-Jun and c-Fos are abundant (32% as average), along with GATA-1 (71% average) in the T. thermophila GST gene promoters. The alignment of all MAPEG (Membrane Associated Proteins involved in Eicosanoid and Glutathione metabolism) GST protein sequences from Tetrahymena species shows that this family is divided into two well-defined clans. The phylogenetic analysis of T. thermophila GSTs has shown that a cluster of 19 Mu-class GST genes are phylogenetic predecessors of members from the omega, theta and zeta classes. This means that the current GST phylogenetic model needs to be modified. Sixteen T. thermophila GST genes, together with two clusters including three genes each with very high identity, have been selected for qRT-PCR analysis under stress from eleven different environmental stressors. This analysis has revealed that there are GST genes that respond selectively and/or differentially to each stressor, independently of the GST class to which it belongs. Most of them respond to the two more toxic metal(loid)s used (Cd or As).]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fgene.2025.1564143</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fgene.2025.1564143</link>
        <title><![CDATA[Corrigendum: Zearalenone exposure enhanced the expression of tumorigenesis genes in donkey granulosa cells via the PTEN/PI3K/AKT signaling pathway]]></title>
        <pubdate>2025-02-17T00:00:00Z</pubdate>
        <category>Correction</category>
        <author>Guo-Liang Zhang</author><author>Jun-Lin Song</author><author>Chuan-Liang Ji</author><author>Yu-Long Feng</author><author>Jie Yu</author><author>Charles M. Nyachoti</author><author>Gong-She Yang</author>
        <description></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fgene.2024.1508521</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fgene.2024.1508521</link>
        <title><![CDATA[SOLA: dissecting dose-response patterns in multi-omics data using a semi-supervised workflow]]></title>
        <pubdate>2024-12-02T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Wanxin Lai</author><author>You Song</author><author>Knut Erik Tollefsen</author><author>Torgeir R. Hvidsten</author>
        <description><![CDATA[An increasing number of ecotoxicological studies have used omics-data to understand the dose-response patterns of environmental stressors. However, very few have investigated complex non-monotonic dose-response patterns with multi-omics data. In the present study, we developed a novel semi-supervised network analysis workflow as an alternative to benchmark dose (BMD) modelling. We utilised a previously published multi-omics dataset generated from Daphnia magna after chronic gamma radiation exposure to obtain novel knowledge on the dose-dependent effects of radiation. Our approach combines 1) unsupervised co-expression network analysis to group genes with similar dose responses into modules; 2) supervised classification of these modules by relevant response patterns; 3) reconstruction of regulatory networks based on transcription factor binding motifs to reveal the mechanistic underpinning of the modules; 4) differential co-expression network analysis to compare the discovered modules across two datasets with different exposure periods; and 5) pathway enrichment analysis to integrate transcriptomics and metabolomics data. Our method unveiled both known and novel effects of gamma radiation, provide insight into shifts in responses from low to high dose rates, and can be used as an alternative approach for multi-omics dose-response analysis in future. The workflow SOLA (Semi-supervised Omics Landscape Analysis) is available at https://gitlab.com/wanxin.lai/SOLA.git.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fgene.2024.1389095</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fgene.2024.1389095</link>
        <title><![CDATA[Integrating gene expression and splicing dynamics across dose-response oxidative modulators]]></title>
        <pubdate>2024-05-22T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>A. Rasim Barutcu</author><author>Michael B. Black</author><author>Raymond Samuel</author><author>Scott Slattery</author><author>Patrick D. McMullen</author><author>Andy Nong</author>
        <description><![CDATA[Toxicological risk assessment increasingly utilizes transcriptomics to derive point of departure (POD) and modes of action (MOA) for chemicals. One essential biological process that allows a single gene to generate several different RNA isoforms is called alternative splicing. To comprehensively assess the role of splicing dysregulation in toxicological evaluation and elucidate its potential as a complementary endpoint, we performed RNA-seq on A549 cells treated with five oxidative stress modulators across a wide dose range. Differential gene expression (DGE) showed limited pathway enrichment except at high concentrations. However, alternative splicing analysis revealed variable intron retention events affecting diverse pathways for all chemicals in the absence of significant expression changes. For instance, diazinon elicited negligible gene expression changes but progressive increase in the number of intron retention events, suggesting splicing alterations precede expression responses. Benchmark dose modeling of intron retention data highlighted relevant pathways overlooked by expression analysis. Systematic integration of splicing datasets should be a useful addition to the toxicogenomic toolkit. Combining both modalities paint a more complete picture of transcriptomic dose-responses. Overall, evaluating intron retention dynamics afforded by toxicogenomics may provide biomarkers that can enhance chemical risk assessment and regulatory decision making. This work highlights splicing-aware toxicogenomics as a possible additional tool for examining cellular responses.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fgene.2024.1393665</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fgene.2024.1393665</link>
        <title><![CDATA[Characteristics of phosgene aspiration lung injury analyzed based on transcriptomics and proteomics]]></title>
        <pubdate>2024-05-17T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Li-Na Wang</author><author>Yi-Ru Shao</author><author>Peng-Fei Wang</author><author>Jiang Lv</author><author>Dai-Kun He</author>
        <description><![CDATA[BackgroundPhosgene is a chemical material widely used worldwide. No effective method has been developed to reverse its pathological injuries. Some studies have shown that neuronal inflammation in lung tissue is involved, but the specific mechanism has not been reported.ObjectiveTo analyze the expression alterations of whole transcriptome gene sequencing bioinformatics and protein expression profile in lung tissue after phosgene aspiration lung injury (P-ALI) and find the main factors and pathways affecting the prognosis of P-ALI.MethodsRat models of P-ALI were made by phosgene. Rats were divided into a P-ALI group and a blank group. Hematoxylin-eosin (HE) staining and lung wet/dry ratio measurement were used to evaluate the lung injury. The levels of inflammatory factors were measured by ELISA. High-throughput sequencing was used to measure the expression profile of each gene. Protein expression profiles were determined by label-free relative quantification of the differential proteome.ResultsLung injury such as the disordered structure of alveolar wall and inflammatory factors (IL-1β, IL-18, and IL-33) were significantly increased in the P-ALI group (p < 0.05). There were 225 differentially expressed lncRNAs, including 85 upregulated and 140 downregulated genes. They were also the genomes with the most significant changes in transcriptome gene expression, mainly constituting cytoplasmic, synaptic structures and transporters, and involved in amino acid and carbon metabolism. There were 42 differentially expressed circRNAs, including 25 upregulated genes and 17 downregulated genes, mainly involved in cell composition, growth, differentiation, and division. There were only 10 differentially expressed miRNAs genes, all upregulated and mainly involved in the inflammatory response pathway. Proteome identification showed 79 differentially expressed proteins. KEGG enrichment analysis showed that it was mainly involved in the N-glycan biosynthesis pathway.ConclusionWe discovered that differentially regulated genes (lncRNAs, circRNAs, and miRNAs) were primarily associated with neuronal reflexes and synaptic signaling, including neurotransmitter transmission, ion signaling pathway conduction, neuronal projection, and synaptic vesicle circulation. They affected inflammatory factors and other metabolic pathways. This finding could be explored in future studies.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fgene.2024.1374791</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fgene.2024.1374791</link>
        <title><![CDATA[Transcriptomic point of departure determination: a comparison of distribution-based and gene set-based approaches]]></title>
        <pubdate>2024-05-09T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Eduardo Costa</author><author>Kamin J. Johnson</author><author>Carl A. Walker</author><author>Jason M. O’Brien</author>
        <description><![CDATA[A key step in assessing the potential human and environmental health risks of industrial and agricultural chemicals is to determine the toxicity point of departure (POD), which is the highest dose level that causes no adverse effect. Transcriptomic POD (tPOD) values have been suggested to accurately estimate toxicity POD values. One step in the most common approach for tPOD determination involves mapping genes to annotated gene sets, a process that might lead to substantial information loss particularly in species with poor gene annotation. Alternatively, methods that calculate tPOD values directly from the distribution of individual gene POD values omit this mapping step. Using rat transcriptome data for 79 molecules obtained from Open TG-GATEs (Toxicogenomics Project Genomics Assisted Toxicity Evaluation System), the hypothesis was tested that methods based on the distribution of all individual gene POD values will give a similar tPOD value to that obtained via the gene set-based method. Gene set-based tPOD values using four different gene set structures were compared to tPOD values from five different individual gene distribution methods. Results revealed a high tPOD concordance for all methods tested, especially for molecules with at least 300 dose-responsive probesets: for 90% of those molecules, the tPOD values from all methods were within 4-fold of each other. In addition, random gene sets based upon the structure of biological knowledge-derived gene sets produced tPOD values with a median absolute fold change of 1.3–1.4 when compared to the original biological knowledge-derived gene set counterparts, suggesting that little biological information is used in the gene set-based tPOD generation approach. These findings indicate using individual gene distributions to calculate a tPOD is a viable and parsimonious alternative to using gene sets. Importantly, individual gene distribution-based tPOD methods do not require knowledge of biological organization and can be applied to any species including those with poorly annotated gene sets.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fgene.2023.1296383</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fgene.2023.1296383</link>
        <title><![CDATA[Mft1, identified from a genome-wide screen of the yeast haploid mutants, mediates cell cycle arrest to counteract quinoxaline-induced toxicity]]></title>
        <pubdate>2024-01-12T00:00:00Z</pubdate>
        <category>Brief Research Report</category>
        <author>Abdallah Alhaj Sulaiman</author><author>Dana E. Al-Ansari</author><author>Reem Ali</author><author>Mustapha Aouida</author><author>Dindial Ramotar</author>
        <description><![CDATA[Quinoxaline is a heterocyclic compound with a two-membered ring structure that undergoes redox cycling to produce toxic free radicals. It has antiviral, antibacterial, antifungal, and antitumor activities. However, the biological functions that are involved in mounting a response against the toxic effects of quinoxaline have not been investigated. Herein, we performed a genome-wide screen using the yeast haploid mutant collection and reported the identification of 12 mutants that displayed varying sensitivity towards quinoxaline. No mutant was recovered that showed resistance to quinoxaline. The quinoxaline-sensitive mutants were deleted for genes that encode cell cycle function, as well as genes that belong to other physiological pathways such as the vacuolar detoxification process. Three of the highly sensitive gene-deletion mutants lack the DDC1, DUN1, and MFT1 genes. While Ddc1 and Dun1 are known to perform roles in the cell cycle arrest pathway, the role of Mft1 remains unclear. We show that the mft1Δ mutant is as sensitive to quinoxaline as the ddc1Δ mutant. However, the double mutant ddc1Δ mft1Δ lacking the DDC1 and MFT1 genes, is extremely sensitive to quinoxaline, as compared to the ddc1Δ and mft1Δ single mutants. We further show that the mft1Δ mutant is unable to arrest in the G2/M phase in response to the drug. We conclude that Mft1 performs a unique function independent of Ddc1 in the cell cycle arrest pathway in response to quinoxaline exposure. This is the first demonstration that quinoxaline exerts its toxic effect likely by inducing oxidative DNA damage causing cell cycle arrest. We suggest that clinical applications of quinoxaline and its derivatives should entail targeting cancer cells with defective cell cycle arrest.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fgene.2023.1213706</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fgene.2023.1213706</link>
        <title><![CDATA[Erratum: 10 Years of Toxicogenomics section in Frontiers in Genetics: Past discoveries and Future Perspectives]]></title>
        <pubdate>2023-05-30T00:00:00Z</pubdate>
        <category>Erratum</category>
        <author>Frontiers Production Office </author>
        <description></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fgene.2023.1168713</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fgene.2023.1168713</link>
        <title><![CDATA[Thallium-induced DNA damage, genetic, and epigenetic alterations]]></title>
        <pubdate>2023-04-20T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Laura Sánchez-Chapul</author><author>Abel Santamaría</author><author>Michael Aschner</author><author>Tao Ke</author><author>Alexey A. Tinkov</author><author>Isaac Túnez</author><author>Laura Osorio-Rico</author><author>Sonia Galván-Arzate</author><author>Edgar Rangel-López</author>
        <description><![CDATA[Thallium (Tl) is a toxic heavy metal responsible for noxious effects in living organisms. As a pollutant, Tl can be found in the environment at high concentrations, especially in industrial areas. Systemic toxicity induced by this toxic metal can affect cell metabolism, including redox alterations, mitochondrial dysfunction, and activation of apoptotic signaling pathways. Recent focus on Tl toxicity has been devoted to the characterization of its effects at the nuclear level, with emphasis on DNA, which, in turn, may be responsible for cytogenetic damage, mutations, and epigenetic changes. In this work, we review and discuss past and recent evidence on the toxic effects of Tl at the systemic level and its effects on DNA. We also address Tl’s role in cancer and its control.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fgene.2023.1145769</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fgene.2023.1145769</link>
        <title><![CDATA[Hepatic gene expression profiles during fed–fasted–refed state in mice]]></title>
        <pubdate>2023-03-03T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Nana Ji</author><author>Liping Xiang</author><author>Bing Zhou</author><author>Yan Lu</author><author>Min Zhang</author>
        <description><![CDATA[Background: Regulation of nutrient status during fasting and refeeding plays an important role in maintaining metabolic homeostasis in the liver. Thus, we investigated the impact of the physiological Fed–Fast–Refed cycle on hepatic gene expression in nutrient-sensitive mice.Methods: We performed transcriptomic analysis of liver samples in fed, fasted and refed groups of mice. Through mRNA-sequencing (RNA-Seq) and miRNA-Seq, we compared fasted and fed states (fasted versus fed cohort) as well as refed and fasted states (refed versus fasted cohort) to detect dynamic alterations of hepatic mRNA–miRNA expression during the fed–fasted–refed cycle.Results: We found dozens of dysregulated mRNAs–miRNAs in the transition from fed to fasted and from fasted to refed states. Gene set enrichment analysis showed that gene expression of the two cohorts shared common pathways of regulation, especially for lipid and protein metabolism. We identified eight significant mRNA and three miRNA clusters that were up–downregulated or down–upregulated during the Fed–Fast–Refed cycle. A protein–protein interaction network of dysregulated mRNAs was constructed and clustered into 22 key modules. The regulation between miRNAs and target mRNAs was presented in a network. Up to 42 miRNA–mRNA-pathway pairs were identified to be involved in metabolism. In lipid metabolism, there were significant correlations between mmu-miR-296-5p and Cyp2u1 and between mmu-miR-novel-chr19_16777 and Acsl3.Conclusion: Collectively, our data provide a valuable resource for the molecular characterization of the physiological Fed–Fast–Refed cycle in the liver.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fgene.2023.1073461</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fgene.2023.1073461</link>
        <title><![CDATA[Blood transcriptome responses to PFOA and GenX treatment in the marsupial biomedical model Monodelphis domestica]]></title>
        <pubdate>2023-02-15T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Wenqi Cao</author><author>Katharine Horzmann</author><author>Bettina Schemera</author><author>Myra Petrofski</author><author>Trisha Kendall</author><author>Jennifer Spooner</author><author>Patricia E. Rynders</author><author>John L. VandeBerg</author><author>Xu Wang</author>
        <description><![CDATA[Introduction: Perfluoroalkyl and poly-fluoroalkyl substances (PFASs) are widely used in industrial and consumer products. Due to their environmental persistence and bioaccumulation, PFASs can be found in the blood of humans and wild animals all over the world. Various fluorinated alternatives such as GenX have been developed to replace the long-chain PFASs, but there is limited information about their potential toxicity.Methods:The current study developed blood culture protocols to assess the response to toxic compounds in the marsupial, Monodelphis domestica. After whole-blood culture conditions were tested and optimized, changes in gene expression in response to PFOA and GenX treatment were assessed.Results: More than 10,000 genes were expressed in the blood transcriptomes with and without treatment. Both PFOA and GenX treatment led to significant changes in the whole blood culture transcriptomes. A total of 578 and 148 differentially expressed genes (DEGs) were detected in the PFOA and GenX treatment groups, 32 of which overlapped. Pathway enrichment analysis revealed that DEGs involved in developmental processes were upregulated after PFOA exposure, while those enriched for metabolic and immune system processes were downregulated. GenX exposure upregulated genes associated with fatty acid transport pathways and inflammatory processes, which is consistent with previous studies using rodent models.Discussion: To our knowledge, this study is the first to investigate the effect of PFASs in a marsupial model. The findings provide supportive evidence for significant transcriptomic alterations, suggesting that this mammalian model may provide a mechanism for exploring the potential toxicity of PFOA and GenX.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fgene.2022.1078050</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fgene.2022.1078050</link>
        <title><![CDATA[Preclinical species gene expression database: Development and meta-analysis]]></title>
        <pubdate>2023-01-17T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Caitlin Krause</author><author>Kinga Suwada</author><author>Eric A. G. Blomme</author><author>Kenneth Kowalkowski</author><author>Michael J. Liguori</author><author>Prathap Kumar Mahalingaiah</author><author>Scott Mittelstadt</author><author>Richard Peterson</author><author>Lauren Rendino</author><author>Andy Vo</author><author>Terry R. Van Vleet</author>
        <description><![CDATA[The evaluation of toxicity in preclinical species is important for identifying potential safety liabilities of experimental medicines. Toxicology studies provide translational insight into potential adverse clinical findings, but data interpretation may be limited due to our understanding of cross-species biological differences. With the recent technological advances in sequencing and analyzing omics data, gene expression data can be used to predict cross species biological differences and improve experimental design and toxicology data interpretation. However, interpreting the translational significance of toxicogenomics analyses can pose a challenge due to the lack of comprehensive preclinical gene expression datasets. In this work, we performed RNA-sequencing across four preclinical species/strains widely used for safety assessment (CD1 mouse, Sprague Dawley rat, Beagle dog, and Cynomolgus monkey) in ∼50 relevant tissues/organs to establish a comprehensive preclinical gene expression body atlas for both males and females. In addition, we performed a meta-analysis across the large dataset to highlight species and tissue differences that may be relevant for drug safety analyses. Further, we made these databases available to the scientific community. This multi-species, tissue-, and sex-specific transcriptomic database should serve as a valuable resource to enable informed safety decision-making not only during drug development, but also in a variety of disciplines that use these preclinical species.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fgene.2022.1069068</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fgene.2022.1069068</link>
        <title><![CDATA[Schizosaccharomyces pombe Grx4, Fep1, and Php4: In silico analysis and expression response to different iron concentrations]]></title>
        <pubdate>2022-12-07T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Alia Ebrahim</author><author>Manal A. Alfwuaires</author><author>Mohammad H. Abukhalil</author><author>Fawaz Alasmari</author><author>Fawad Ahmad</author><author>Rui Yao</author><author>Ying Luo</author><author>Ying Huang</author>
        <description><![CDATA[Due to iron’s essential role in cellular metabolism, most organisms must maintain their homeostasis. In this regard, the fission yeast Schizosaccharomyces pombe (sp) uses two transcription factors to regulate intracellular iron levels: spFep1 under iron-rich conditions and spPhp4 under iron-deficient conditions, which are controlled by spGrx4. However, bioinformatics analysis to understand the role of the spGrx4/spFep1/spPhp4 axis in maintaining iron homeostasis in S. pombe is still lacking. Our study aimed to perform bioinformatics analysis on S. pombe proteins and their sequence homologs in Aspergillus flavus (af), Saccharomyces cerevisiae (sc), and Homo sapiens (hs) to understand the role of spGrx4, spFep1, and spPhp4 in maintaining iron homeostasis. The three genes’ expression patterns were also examined at various iron concentrations. A multiple sequence alignment analysis of spGrx4 and its sequence homologs revealed a conserved cysteine residue in each PF00085 domain. Blast results showed that hsGLRX3 is most similar to spGrx4. In addition, spFep1 is most closely related in sequence to scDal80, whereas scHap4 is most similar to spFep1. We also found two highly conserved motifs in spFep1 and its sequence homologs that are significant for iron transport systems because they contain residues involved in iron homeostasis. The scHap4 is most similar to spPhp4. Using STRING to analyze protein-protein interactions, we found that spGrx4 interacts strongly with spPhp4 and spFep1. Furthermore, spGrx4, spPhp4, and spFep1 interact with spPhp2, spPhp3, and spPhp5, indicating that the three proteins play cooperative roles in iron homeostasis. At the highest level of Fe, spgrx4 had the highest expression, followed by spfep1, while spphp4 had the lowest expression; a contrast occurred at the lowest level of Fe, where spgrx4 expression remained constant. Our findings support the notion that organisms develop diverse strategies to maintain iron homeostasis.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fgene.2022.1047746</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fgene.2022.1047746</link>
        <title><![CDATA[Exposure to endosulfan can cause long term effects on general biology, including the reproductive system of mice]]></title>
        <pubdate>2022-11-24T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Anju Sharma</author><author>Arigesavan Kaninathan</author><author>Sumedha Dahal</author><author>Susmita Kumari</author><author>Bibha Choudhary</author><author>Sathees C. Raghavan</author>
        <description><![CDATA[Increased infertility in humans is attributed to the increased use of environmental chemicals in the last several decades. Various studies have identified pesticides as one of the causes of reproductive toxicity. In a previous study, infertility was observed in male mice due to testicular atrophy and decreased sperm count when a sublethal dose of endosulfan (3 mg/kg) with a serum concentration of 23 μg/L was used. However, the serum concentration of endosulfan was much higher (up to 500 μg/L) in people living in endosulfan-exposed areas compared to the one used in the investigation. To mimic the situation in an experimental setup, mice were exposed to 5 mg/kg body weight of endosulfan, and reproductive toxicity and long-term impact on the general biology of animals were examined. HPLC analysis revealed a serum concentration of ∼50 μg/L of endosulfan after 24 h endosulfan exposure affected the normal physiology of mice. Histopathological studies suggest a persistent, severe effect on reproductive organs where vacuole degeneration of basal germinal epithelial cells and degradation of the interstitial matrix were observed in testes. Ovaries showed a reduction in the number of mature Graafian follicles. At the same time, mild vacuolation in liver hepatocytes and changes in the architecture of the lungs were observed. Endosulfan exposure induced DNA damage and mutations in germ cells at the molecular level. Interestingly, even after 8 months of endosulfan exposure, we observed increased DNA breaks in reproductive tissues. An increased DNA Ligase III expression was also observed, consistent with reported elevated levels of MMEJ-mediated repair. Further, we observed the generation of tumors in a few of the treated mice with time. Thus, the study not only explores the changes in the general biology of the mice upon exposure to endosulfan but also describes the molecular mechanism of its long-term effects.]]></description>
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