Current opinion in toxicology最新文献

Defining mechanisms of immunotoxicity is complicated by the many cell types that comprise the immune system, their phenotypic heterogeneity, distribution in tissues throughout the body, and complexity of in vivo interactions. Single-cell RNA-sequencing (scRNA-seq) methods hold promise for determining how chemical exposures alter gene expression and phenotype of individual immune cell phenotypes, leading to adverse effects on immune function. Using arsenic as a case study, this review will examine challenges in defining mechanisms of immunotoxicity and highlight findings from recent studies that have addressed immunotoxicological questions with scRNA-seq. Advancements in immunotherapeutic development driven by single-cell sequencing technologies will be discussed, along with how these state-of-the art methods may be applied to accelerate immunotoxicity testing in future studies. We will finally consider how cell-type-specific gene expression data can be leveraged to glean immune profiles from existing gene expression data, improving our understanding of immunotoxicity and ability to assess the health impacts of immunotoxic chemicals.

Breast cancer is a heterogeneous suite of diseases, with likely strong, but still poorly understood, environmental etiologies. New advances in single cell methods are now poised to help us understand how environmental exposures, such as air and water pollutants, diet, personal and consumer care products, and social factors, may promote the development of aggressive breast cancers. In this review, we describe how dissociated and spatial single cell transcriptomic analyses can be used to advance our understanding how our environment impacts breast carcinogenesis through the view of frameworks such as the Hallmarks of Cancer and the Key Characteristics of Carcinogens.

Neurotoxicological research faces the challenge of linking biological changes resulting from exposures to neuronal function. An additional challenge is understanding cell-type-specific differences and selective vulnerabilities of distinct neuronal populations to toxic insults. Single-cell RNA-sequencing (scRNA-seq) allows for measurement of the transcriptome of individual cells. This makes it a valuable tool for validating and characterizing cell types present in multi-cell type samples in complex tissue or cell culture models, but also for understanding how different cell types respond to toxic insults. Pathway analysis of differentially expressed genes can provide in-depth insights into underlying cell-type-specific mechanisms of neurotoxicity. Toxicological data often has to be translated to outcomes for human health which requires an understanding of inter-species differences. Transcriptomic data aids in understanding these differences, including understanding the developmental timelines of different species. We believe that scRNA-seq holds exciting promises for future neurotoxicological research.

The lung is constantly exposed to a myriad of exogenous stressors. Ground-level ozone represents a ubiquitous and extremely reactive anthropogenic toxicant, impacting the health of millions across the globe. While abundant, epidemiological, in vivo, and in vitro data focuses the ozone toxicity in individual cell types (e.g. epithelial type II, alveolar macrophages) or signaling pathways involved in the injury (e.g. akt, glutathione). When appropriately used, bulk and single-cell RNA sequencing techniques have the potential to provide complete, and in certain cases unbiased, information of the molecular events taking place in the steady-state and injured lung, and even capture the phenotypic diversity of neighboring cells. To this end, this review compiles information pertaining to the latest understanding of lung cell identity and activation in the steady-state and ozone-exposed lung. In addition, it discusses the value and benefits of multi-omics approaches and other tools developed to predict cell–cell communication and dissect spatial heterogeneity.

Toxicogenomics is a subdiscipline of toxicology that assesses the toxicity using a combination of genomics, advanced computational technologies, and other high-throughput techniques. In the last few years, the rapid evolution of technologies such as transcriptomics, proteomics, metabolomics, and computational technologies allowed the application of a more flexible strategy for the risk assessment due to exposure to chemical and xenobiotic substances. The integration of bioinformatics approaches with novel genomic technologies permits extraordinary advancements in different fields of biology, toxicology, medicine, and, in particular, in occupational medicine, making accessible a “personalized” approach to this discipline. The scope of this paper is to investigate the recent trend of genomic toxicology in combination with bioinformatics approaches and its novel application in toxicological studies with reference to our experience and findings. In particular, it is shown how the dose biomarkers, the pollutants urine metabolites in our case, allow a precise exposure assessment whilst effect biomarkers can be individuated, significantly associated with the former. Among the effect biomarkers, our experience is mainly focused on oxidative stress biomarkers and miRNA profiles. Finally, it is shown how the early effect biomarkers are dysregulated when specific clinical outcomes are occurring. This early dysregulation can be used as individual susceptibility biomarker.