Strain-related differences in mouse lung gene expression over a two-year period of inhalation exposure to styrene: Relevance to human risk assessment

Regulatory Toxicology and Pharmacology : RTP
Melvin E AndersenPatrick D McMullen

Abstract

Both CD-1 and C57BL/6 wildtype (C57BL/6-WT) mice show equivalent short-term lung toxicity from exposures to styrene, while long-term tumor responses are greater in CD-1 mice. We analyzed lung gene expression from styrene exposures lasting from 1-day to 2-years in male mice from these two strains, including a Cyp2f2(-/-) knockout (C57BL/6-KO) and a Cyp2F1/2A13/2B6 transgenic mouse (C57BL/6-TG). With short term exposures (1-day to 1-week), CD-1 and C57BL/6-WT mice had thousands of differentially expressed genes (DEGs), consistent with changes in pathways for cell proliferation, cellular lipid metabolism, DNA-replication and inflammation. C57BL/6-WT mice responded within a single day; CD-1 mice required several days of exposure. The numbers of exposure related DEGs were greatly reduced at longer times (4-weeks to 2-years) with enrichment only for biological oxidations in C57BL/6-WT and metabolism of lipids and lipoproteins in CD-1. Gene expression results indicate a non-genotoxic, mouse specific mode of action for short-term styrene responses related to activation of nuclear receptor signaling and cell proliferation. Greater tumor susceptibility in CD-1 mice correlated with the presence of the Pas1 loci, differential Cytochrome P4...Continue Reading

Citations

May 27, 2020·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·Samuel M CohenJames S Bus
Feb 13, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Melvin E Andersen, James S Bus
Jul 10, 2019·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·M I BantonS S Sarang
Jan 14, 2021·Scientific Reports·Nayra CárdenesMauricio Rojas
Oct 20, 2019·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Patrick D McMullenMelvin E Andersen
Jun 27, 2021·Regulatory Toxicology and Pharmacology : RTP·Susan J BorghoffGrace A Chappell

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