Editorial overview of the special issue on genomic toxicology epigenetics

Rusyn, Ivan; Pogribny, Igor P.

doi:10.1016/j.cotox.2017.11.006

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“…Accumulating evidence suggests that environmental chemicals may alter the epigenome by disrupting cytosine DNA methylation patterns, chromatin structure and expression of noncoding RNAs (Baccarelli and Bollati 2009;Chappell et al 2016;Rusyn and Pogribny 2017). Epigenetic reprogramming has been linked to genomic instability, a hallmark of cancer (Hanahan and Weinberg 2011), and induction of epigenetic alterations is one of key mechanistic characteristics of known human carcinogens (Smith et al 2016).…”

Section: Introductionmentioning

confidence: 99%

Sex-specific differences in genotoxic and epigenetic effects of 1,3-butadiene among mouse tissues

et al. 2018

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Exposure to environmental chemicals has been shown to have an impact on the epigenome. One example is a known human carcinogen 1,3-butadiene which acts primarily by a genotoxic mechanism, but also disrupts the chromatin structure by altering patterns of cytosine DNA methylation and histone modifications. Sex-specific differences in 1,3-butadiene-induced genotoxicity and carcinogenicity are well established; however, it remains unknown whether 1,3butadiene-associated epigenetic alterations are also sex-dependent. Therefore, we tested the hypothesis that inhalational exposure to 1,3-butadiene will result in sex-specific epigenetic alterations. DNA damage and epigenetic effects of 1,3-butadiene were evaluated in in liver, lung, and kidney tissues of male and female mice of two inbred strains (C57BL/6J and CAST/EiJ). Mice were exposed to 0 or 425 ppm of 1,3-butadiene by inhalation (6 hr/day, 5 days/week) for 2 weeks. Strain-and tissue-specific differences in 1,3-butadiene-induced DNA adducts and crosslinks we detected in the liver, lung and kidney; however, significant sex-specific differences in DNA damage were observed in the lung of C57BL/6J mice only. In addition, we assessed expression of the DNA repair genes and observed a marked up-regulation of Mgmt in the kidney in female C57BL/6J mice. Sex-specific epigenetic effects of 1,3-butadiene exposure were evident in alterations of cytosine DNA methylation and histone modifications in the liver and lung in both strains. Specifically, we observed a loss of cytosine DNA methylation in the liver and lung of male and female 1,3-butadiene-exposed C57BL/6J mice, whereas hypermethylation was found in the liver and lung in 1,3-butadiene-exposed female CAST/EiJ mice. Our findings suggest that strain and sex-specific effects of 1,3-butadiene on the epigenome may contribute to the known differences in cancer susceptibility.

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