Epigenetic Events Determine Tissue-Specific Toxicity of Inhalational Exposure to the Genotoxic Chemical 1,3-Butadiene in Male C57BL/6J Mice

摘要: Butadiene (BD), a widely used industrial chemical and ubiquitous environmental pollutant, is known human carcinogen. Although genotoxicity an established mechanism of the tumorigenicity BD, epigenetic effects have also been observed in livers mice exposed to chemical. To better characterize diverse molecular mechanisms BD tumorigenicity, we evaluated genotoxic epigenotoxic exposure mouse tissues that are target (lung liver) non-target (kidney) for BD-induced tumors. We hypothesized alterations may explain, at least part, tissue-specific differences mice. level N-7-(2,3,4-trihydroxybut-1- yl)guanine adducts 1,4-bis-(guan-7-yl)-2,3-butanediol crosslinks, DNA methylation, histone modifications male C57BL/6 filtered air or 425 ppm by inhalation (6 h/day, 5 days/week) 2 weeks. damage was all three BD-exposed mice, variation clearly existed between kidneys, liver, lungs. Epigenetic indicative genomic instability, including demethylation repetitive sequences histone-lysine acetylation, were evident liver lung Changes methylation insignificant kidneys treated whereas marks condensed heterochromatin transcriptional silencing (histone-lysine trimethylation) increased. These represent potential mechanistic explanation lack tumorigenesis kidney. Our results indicate differential tissue susceptibility chemical-induced be attributed alterations.