Assessing molecular initiating events (MIEs), key events (KEs) and modulating factors (MFs) for styrene responses in mouse lungs using whole genome gene expression profiling following 1-day and multi-week exposures

• Published in: Toxicology and applied pharmacology Vol. 335; pp. 28 - 40
• Main Authors: Andersen, Melvin E., Cruzan, George, Black, Michael B., Pendse, Salil N., Dodd, Darol, Bus, James S., Sarang, Satinder S., Banton, Marcy I., Waites, Robbie, McMullen, Patrick D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.11.2017
• Subjects: Adaptation and modulating factors; Animals; Aryl Hydrocarbon Hydroxylases - genetics; Aryl Hydrocarbon Hydroxylases - metabolism; Circadian Rhythm - drug effects; Circadian Rhythm - genetics; Circadian Rhythm Signaling Peptides and Proteins - genetics; Circadian Rhythm Signaling Peptides and Proteins - metabolism; Cytochrome P-450 CYP2B6 - genetics; Cytochrome P-450 CYP2B6 - metabolism; Cytochrome P-450 Enzyme System - deficiency; Cytochrome P-450 Enzyme System - genetics; Cytochrome P450 Family 2 - genetics; Cytochrome P450 Family 2 - metabolism; Dose-Response Relationship, Drug; Gene Expression Profiling - methods; Gene Regulatory Networks - drug effects; Genotype; Inhalation Exposure - adverse effects; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Lung - drug effects; Lung - metabolism; Male; Mice, Inbred C57BL; Mice, Knockout; MIEs; Models, Animal; Molecular initiating events; Mouse lung tumors; Nr4 family gene downregulation; Phenotype; Signal Transduction - drug effects; Signal Transduction - genetics; Styrene inhalation; Styrenes - metabolism; Styrenes - toxicity; Time Factors; Toxicogenetics - methods; Transcription Factors - genetics; Transcription Factors - metabolism; Transcriptome - drug effects; Molecular initiating events; Styrene inhalation; MIEs; Mouse lung tumors; Nr4 family gene downregulation; Adaptation and modulating factors

Styrene increased lung tumors in mice at chronic inhalation exposures of 20ppm and greater. MIEs, KEs and MFs were examined using gene expression in three strains of male mice (the parental C57BL/6 strain, a CYP2F2(−/−) knock out and a CYP2F2(−/−) transgenic containing human CYP2F1, 2A13 and 2B6). E...