The application of transcriptional benchmark dose modeling for deriving thresholds of effects associated with solar-simulated ultraviolet radiation exposure

Environmental and Molecular Mutagenesis
Sami S QutobB B Gollapudi

Abstract

Considerable data has been generated to elucidate the transcriptional response of cells to ultraviolet radiation (UVR) exposure providing a mechanistic understanding of UVR-induced cellular responses. However, using these data to support standards development has been challenging. In this study, we apply benchmark dose (BMD) modeling of transcriptional data to derive thresholds of gene responsiveness following exposure to solar-simulated UVR. Human epidermal keratinocytes were exposed to three doses (10, 20, 150 kJ/m2 ) of solar simulated UVR and assessed for gene expression changes 6 and 24 hr postexposure. The dose-response curves for genes with p-fit values (≥ 0.1) were used to derive BMD values for genes and pathways. Gene BMDs were bi-modally distributed, with a peak at ∼16 kJ/m2 and ∼108 kJ/m2 UVR exposure. Genes/pathways within Mode 1 were involved in cell signaling and DNA damage response, while genes/pathways in the higher Mode 2 were associated with immune response and cancer development. The median value of each Mode coincides with the current human exposure limits for UVR and for the minimal erythemal dose, respectively. Such concordance implies that the use of transcriptional BMD data may represent a promising new ...Continue Reading

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Citations

Jul 21, 2020·International Journal of Radiation Biology·Vinita ChauhanRobert Stainforth
Jun 17, 2021·International Journal of Radiation Biology·Vinita ChauhanDebora Quayle
Sep 3, 2021·Developmental Cell·Meng-Yen LiElena Ezhkova

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Methods Mentioned

BETA
gene probe
ubiquitination

Software Mentioned

BMDExpress Data Viewer
Multiple Dataset Comparison
Google Chart
BMDExpress
Illumina GenomeStudio
Ingenuity Pathway Analysis

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