Environmental Carcinogenesis at the Single-Cell Level.

Elucidating the mechanisms behind how exposure to environmental chemicals can lead to cancer is not easy due to the complex natures of these compounds and the challenges to establish biologically relevant experimental models to study them. Environmental chemicals often present selective mechanisms of action on different cell types and can be involved in the modulation of targeted cells and their microenvironment, including immune cells. Currently, the limitations of traditional epidemiologic correlation analyses, cell-based assays, and animal models are that they are unable to comprehensively examine cellular heterogeneity and the tissue-selective influences. To this end, we propose utilizing single-cell RNA-sequencing (scRNA-seq) to more effectively capture the subtle and complex effects of environmental chemicals and how their exposure could lead to cancer. scRNA-seq's capabilities for studying gene expression level data at a significantly higher resolution relative to bulk RNA-sequencing (RNA-seq) enable studies to evaluate how environmental chemicals regulate gene transcription on different cell types as well as how these compounds impact signaling pathways and interactions between cells in the tissue microenvironment. These studies will be valuable for evaluating environmental chemicals' carcinogenic properties at the individual cell level.