Advertisement

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

  • Lauren Lewis
  • Grace A. Chappell
  • Tetyana Kobets
  • Bridget E. O’Brian
  • Dewakar Sangaraju
  • Oksana Kosyk
  • Wanda Bodnar
  • Natalia Y. Tretyakova
  • Igor P. Pogribny
  • Ivan RusynEmail author
Genotoxicity and Carcinogenicity
  • 159 Downloads

Abstract

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 1,3-butadiene-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 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 h/day, 5 days/week) for 2 weeks. Strain- and tissue-specific differences in 1,3-butadiene-induced DNA adducts and crosslinks were 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 upregulation 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.

Keywords

Butadiene Epigenetic Mouse Liver Lung Kidney 

Notes

Acknowledgements

This work was supported, in part, by grants from National Institutes of Health (R01 ES023195, R01 CA095039 and P30 ES025128). The views expressed in this article are those of the authors and do not necessarily reflect the views of NIH.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

204_2018_2374_MOESM1_ESM.docx (11 kb)
Supplementary material 1 (DOCX 11 KB)

References

  1. Arif JM, Dresler C, Clapper ML et al (2006) Lung DNA adducts detected in human smokers are unrelated to typical polyaromatic carcinogens. Chem Res Toxicol 19(2):295–299PubMedCrossRefGoogle Scholar
  2. Baccarelli A, Bollati V (2009) Epigenetics and environmental chemicals. Curr Opin Pediatr 21(2):243–251PubMedPubMedCentralCrossRefGoogle Scholar
  3. Bae JM, Shin SH, Kwon HJ et al (2012) ALU and LINE-1 hypomethylations in multistep gastric carcinogenesis and their prognostic implications. Int J Cancer 131(6):1323–1331PubMedCrossRefGoogle Scholar
  4. Baylin SB, Herman JG (2000) DNA hypermethylation in tumorigenesis: epigenetics joins genetics. Trends Genet 16(4):168–174PubMedCrossRefGoogle Scholar
  5. Chappell G, Kobets T, O’Brien B et al (2014) Epigenetic events determine tissue-specific toxicity of inhalational exposure to the genotoxic chemical 1,3-butadiene in male C57BL/6J mice. Toxicol Sci 142(2):375–384PubMedPubMedCentralCrossRefGoogle Scholar
  6. Chappell G, Pogribny IP, Guyton KZ, Rusyn I (2016) Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review. Mutat Res Rev Mutat Res 768:27–45PubMedPubMedCentralCrossRefGoogle Scholar
  7. Chappell GA, Israel JW, Simon JM et al (2017) Variation in DNA-damage responses to an inhalational carcinogen (1,3-butadiene) in relation to strain-specific differences in chromatin accessibility and gene transcription profiles in C57BL/6J and CAST/EiJ mice. Environ Health Perspect 125(10):107006PubMedPubMedCentralCrossRefGoogle Scholar
  8. Clayton JA, Collins FS (2014) Policy: NIH to balance sex in cell and animal studies. Nature 509(7500):282–283PubMedPubMedCentralCrossRefGoogle Scholar
  9. Cogliano VJ, Baan R, Straif K et al (2011) Preventable exposures associated with human cancers. J Natl Cancer Inst 103(24):1827–1839PubMedPubMedCentralCrossRefGoogle Scholar
  10. Dumenco LL, Allay E, Norton K, Gerson SL (1993) The prevention of thymic lymphomas in transgenic mice by human O6-alkylguanine-DNA alkyltransferase. Science 259(5092):219–222PubMedCrossRefGoogle Scholar
  11. Faulk C, Barks A, Liu K, Goodrich JM, Dolinoy DC (2013) Early-life lead exposure results in dose- and sex-specific effects on weight and epigenetic gene regulation in weanling mice. Epigenomics 5(5):487–500PubMedCrossRefGoogle Scholar
  12. Goggin M, Swenberg JA, Walker VE, Tretyakova N (2009) Molecular dosimetry of 1,2,3,4-diepoxybutane-induced DNA-DNA cross-links in B6C3F1 mice and F344 rats exposed to 1,3-butadiene by inhalation. Cancer Res 69(6):2479–2486PubMedPubMedCentralCrossRefGoogle Scholar
  13. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674PubMedPubMedCentralCrossRefGoogle Scholar
  14. Hartman JH, Miller GP, Caro AA et al (2017) 1,3-Butadiene-induced mitochondrial dysfunction is correlated with mitochondrial CYP2E1 activity in Collaborative Cross mice. Toxicology 378:114–124PubMedPubMedCentralCrossRefGoogle Scholar
  15. Hossain K, Suzuki T, Hasibuzzaman MM et al (2017) Chronic exposure to arsenic, LINE-1 hypomethylation, and blood pressure: a cross-sectional study in Bangladesh. Environ Health 16(1):20PubMedPubMedCentralCrossRefGoogle Scholar
  16. IARC (2009) 1,3-Butadiene, ethylene oxide and vinyl halides (vinyl fluoride and vinyl bromide). WHO, LyonGoogle Scholar
  17. Israel JW, Chappell GA, Simon JM et al (2018) Tissue- and strain-specific effects of a genotoxic carcinogen 1,3-butadiene on chromatin and transcription. Mamm Genome 29(1–2):153–167PubMedCrossRefGoogle Scholar
  18. Khobta A, Epe B (2012) Interactions between DNA damage, repair, and transcription. Mutation Res 736(1–2):5–14PubMedCrossRefGoogle Scholar
  19. Kippler M, Engstrom K, Mlakar SJ et al (2013) Sex-specific effects of early life cadmium exposure on DNA methylation and implications for birth weight. Epigenetics 8(5):494–503PubMedPubMedCentralCrossRefGoogle Scholar
  20. Koturbash I, Scherhag A, Sorrentino J et al (2011) Epigenetic mechanisms of mouse interstrain variability in genotoxicity of the environmental toxicant 1,3-butadiene. Toxicol Sci 122(2):448–456PubMedPubMedCentralCrossRefGoogle Scholar
  21. Kovalchuk O, Burke P, Besplug J, Slovack M, Filkowski J, Pogribny I (2004) Methylation changes in muscle and liver tissues of male and female mice exposed to acute and chronic low-dose X-ray-irradiation. Mutat Res 548(1–2):75–84PubMedCrossRefGoogle Scholar
  22. Kundakovic M, Gudsnuk K, Franks B et al (2013) Sex-specific epigenetic disruption and behavioral changes following low-dose in utero bisphenol A exposure. Proc Natl Acad Sci USA 110(24):9956–9961PubMedCrossRefGoogle Scholar
  23. Liu EY, Russ J, Wu K et al (2014) C9orf72 hypermethylation protects against repeat expansion-associated pathology in ALS/FTD. Acta Neuropathol 128(4):525–541PubMedPubMedCentralCrossRefGoogle Scholar
  24. Martens JH, O’Sullivan RJ, Braunschweig U et al (2005) The profile of repeat-associated histone lysine methylation states in the mouse epigenome. EMBO J 24(4):800–812PubMedPubMedCentralCrossRefGoogle Scholar
  25. Melnick RL, Huff J, Matanoski GM (1992) Carcinogenicity of 1,3-butadiene. Lancet 340:724–725PubMedCrossRefGoogle Scholar
  26. Meng Q, Walker DM, McDonald JD et al (2007) Age-, gender-, and species-dependent mutagenicity in T cells of mice and rats exposed by inhalation to 1,3-butadiene. Chem Biol Interact 166(1–3):121–131PubMedCrossRefGoogle Scholar
  27. National Toxicology Program (1993) NTP toxicology and carcinogenesis studies of 1,3-Butadiene (CAS No. 106-99-0) in B6C3F1 Mice (inhalation studies). Natl Toxicol Program Tech Rep Ser 434:1–389Google Scholar
  28. Owen PE, Glaister JR, Gaunt IF, Pullinger DH (1987) Inhalation toxicity studies with 1,3-butadiene. 3. Two year toxicity/carcinogenicity study in rats. Am Ind Hyg Assoc J 48(5):407–413PubMedCrossRefGoogle Scholar
  29. Patchsung M, Settayanon S, Pongpanich M, Mutirangura D, Jintarith P, Mutirangura A (2018) Alu siRNA to increase Alu element methylation and prevent DNA damage. Epigenomics 10(2):175–185PubMedCrossRefGoogle Scholar
  30. Pogribny IP, Beland FA (2009) DNA hypomethylation in the origin and pathogenesis of human diseases. Cell Mol Life Sci 66(14):2249–2261PubMedCrossRefGoogle Scholar
  31. Pogribny IP, Rusyn I (2013) Environmental toxicants, epigenetics, and cancer. Adv Exp Med Biol 754:215–232PubMedPubMedCentralCrossRefGoogle Scholar
  32. Pogribny I, Raiche J, Slovack M, Kovalchuk O (2004) Dose-dependence, sex- and tissue-specificity, and persistence of radiation-induced genomic DNA methylation changes. Biochem Bioph Res Co 320(4):1253–1261CrossRefGoogle Scholar
  33. Pogribny IP, Ross SA, Tryndyak VP, Pogribna M, Poirier LA, Karpinets TV (2006) Histone H3 lysine 9 and H4 lysine 20 trimethylation and the expression of Suv4-20h2 and Suv-39h1 histone methyltransferases in hepatocarcinogenesis induced by methyl deficiency in rats. Carcinogenesis 27(6):1180–1186PubMedCrossRefGoogle Scholar
  34. Primavera A, Fustinoni S, Biroccio A et al (2008) Glutathione transferases and glutathionylated hemoglobin in workers exposed to low doses of 1,3-butadiene. Cancer Epidemiol Biomark Prev 17(11):3004–3012CrossRefGoogle Scholar
  35. Robertson KD (2005) DNA methylation and human disease. Nat Rev Genet 6(8):597–610PubMedCrossRefGoogle Scholar
  36. Rusyn I, Pogribny IP (2017) Editorial overview of the special issue on genomic toxicology epigenetics. Curr Opin Toxicol 6:i-iiiPubMedPubMedCentralGoogle Scholar
  37. Rusyn I, Asakura S, Pachkowski B et al (2004) Expression of base excision DNA repair genes is a sensitive biomarker for in vivo detection of chemical-induced chronic oxidative stress: identification of the molecular source of radicals responsible for DNA damage by peroxisome proliferators. Cancer Res 64(3):1050–1057PubMedCrossRefGoogle Scholar
  38. Rusyn I, Kleeberger SR, McAllister KA, French JE, Svenson KL (2018) Introduction to mammalian genome special issue: the combined role of genetics and environment relevant to human disease outcomes. Mamm Genome 29(1–2):1–4PubMedCrossRefGoogle Scholar
  39. Sangaraju D, Goggin M, Walker V, Swenberg J, Tretyakova N (2012) NanoHPLC-nanoESI(+)-MS/MS quantitation of bis-N7-guanine DNA-DNA cross-links in tissues of B6C3F1 mice exposed to subppm levels of 1,3-butadiene. Anal Chem 84(3):1732–1739PubMedPubMedCentralCrossRefGoogle Scholar
  40. Smith MT, Guyton KZ, Gibbons CF et al (2016) Key characteristics of carcinogens as a basis for organizing data on mechanisms of carcinogenesis. Environ Health Perspect 124(6):713–721PubMedCrossRefGoogle Scholar
  41. Swenberg JA, Ham AJ, Koc H et al (2000) DNA adducts: effects of low exposure to ethylene oxide, vinyl chloride and butadiene. Mutat Res 464(1):77–86PubMedCrossRefGoogle Scholar
  42. Swenberg JA, Bordeerat NK, Boysen G et al (2011) 1,3-Butadiene: biomarkers and application to risk assessment. Chem Biol Interact 24(6):809–817Google Scholar
  43. Thomson JP, Moggs JG, Wolf CR, Meehan RR (2014) Epigenetic profiles as defined signatures of xenobiotic exposure. Mutat Res Genet Toxicol Environ Mutagen 764–765:3–9PubMedCrossRefGoogle Scholar
  44. Tryndyak V, Kindrat I, Dreval K, Churchwell MI, Beland FA, Pogribny IP (2018) Effect of aflatoxin B1, benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol 121:214–223PubMedCrossRefGoogle Scholar
  45. Tubbs JL, Pegg AE, Tainer JA (2007) DNA binding, nucleotide flipping, and the helix-turn-helix motif in base repair by O6-alkylguanine-DNA alkyltransferase and its implications for cancer chemotherapy. DNA Repair 6(8):1100–1115PubMedPubMedCentralCrossRefGoogle Scholar
  46. Vacek PM, Albertini RJ, Sram RJ, Upton P, Swenberg JA (2010) Hemoglobin adducts in 1,3-butadiene exposed Czech workers: female-male comparisons. Chem Biol Interact 188(3):668–676PubMedCrossRefGoogle Scholar
  47. Valinluck V, Tsai HH, Rogstad DK, Burdzy A, Bird A, Sowers LC (2004) Oxidative damage to methyl-CpG sequences inhibits the binding of the methyl-CpG binding domain (MBD) of methyl-CpG binding protein 2 (MeCP2). Nucleic Acids Res 32(14):4100–4108PubMedPubMedCentralCrossRefGoogle Scholar
  48. Yoder JA, Walsh CP, Bestor TH (1997) Cytosine methylation and the ecology of intragenomic parasites. Trends Genet 13(8):335–340PubMedCrossRefGoogle Scholar
  49. Zhang X, Hou H, Chen H, Liu Y, Wang A, Hu Q (2015) A column-switching LC-MS/MS method for simultaneous quantification of biomarkers for 1,3-butadiene exposure and oxidative damage in human urine. J Chromatogr B Analyt Technol Biomed Life Sci 1002:123–129PubMedCrossRefGoogle Scholar
  50. Zuo J, Brewer DS, Arlt VM, Cooper CS, Phillips DH (2014) Benzo pyrene-induced DNA adducts and gene expression profiles in target and non-target organs for carcinogenesis in mice. BMC Genom 15:880CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Lauren Lewis
    • 1
  • Grace A. Chappell
    • 1
  • Tetyana Kobets
    • 2
  • Bridget E. O’Brian
    • 2
  • Dewakar Sangaraju
    • 3
  • Oksana Kosyk
    • 2
  • Wanda Bodnar
    • 2
  • Natalia Y. Tretyakova
    • 3
  • Igor P. Pogribny
    • 4
  • Ivan Rusyn
    • 1
    Email author
  1. 1.Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical SciencesTexas A&M UniversityCollege StationUSA
  2. 2.Department of Environmental Sciences and EngineeringUniversity of North CarolinaChapel HillUSA
  3. 3.Department of Medicinal ChemistryUniversity of MinnesotaMinneapolisUSA
  4. 4.Division of Biochemical ToxicologyNational Center for Toxicological Research, Food and Drug AdministrationJeffersonUSA

Personalised recommendations