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Significance Cells change their mRNA expression in response to biologically active substances in a dose-dependent manner. Because different genes in a cell show distinct sensitivities to the same substance, changes in the genome-wide mRNA expression profile induced by low and high doses of a substance are essentially different, but this notion has been commonly overlooked in previously published studies. Using a human cell culture model and microarray, we performed genome-wide determinations of gene sensitivities to hormonally active substances with statistically rigorous approaches. Our study provides a conceptual and methodological framework for the systematic examination of gene sensitivities and demonstrates effective detection of nonmonotonic dose-dependent responses, introducing the importance of gene sensitivity analysis to pharmacogenomic and toxicogenomic research.

Expressomal approach for comprehensive analysis and visualization of ligand sensitivities of xenoestrogen responsive genes