Species Differences in DNA Damage by Butadiene: Role of Diepoxybutane

  • B. Jelitto
  • R. R. Vangala
  • R. J. Laib
Conference paper
Part of the Archives of Toxicology book series (TOXICOLOGY, volume 13)

Abstract

In microsomal incubates 1,3-butadiene (BD) is metabolized by cytochrome P- 450 to its epoxide 1,2-epoxybutene (EB). Further metabolic transformation of the epoxide intermediate by epoxide hydrolase and/or monoxygenase would lead to 3,4-epoxy-1,2-butanediol (via 3-butene-l,2-diol) and to diepoxybutane (DEB, Malvoisin and Roberfroid 1982; Laib et al 1988). Remarkable species differences in the carcinogenic potency of BD between rats (Sprague-Dawley) and mice (B6C3F1) have been demonstrated (Huff et al 1985). The increased susceptibility of mice to BD-induced carcinogenesis has been attributed to the higher metabolic rate of BD, limited detoxification of EB and to the resulting accumulation of reactive epoxide intermediates in this species (Kreiling et al 1987; Laib et al 1988). To investigate comparatively the role of EB and DEB in BD-induced carcinogenesis in both species, studies on alkylation and alkaline filter elution of DNA were carried out in mice and rats.

Keywords

Hydrolysis Adduct Vinyl Hydroxyapatite Epoxide 

Abbreviations

BD

butadiene

EB

epoxybutene

DEB

diepoxybutane

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Beland FA, Dooley KL, Casciano DA (1979). Rapid isolation of carcinogen-bound DNA and RNA by hydroxyapatite chromatography. J Chromatogr 174: 177–186PubMedCrossRefGoogle Scholar
  2. Citti L, Gervasi PG, Turchi G, Belluci G, Bianchini R (1984) The reaction of 3,4-epoxy-1-butene with deoxyguanosine and DNA in vitro: synthesis and characterization of the main adducts. Carcinogenesis 5: 47–52PubMedCrossRefGoogle Scholar
  3. Huff JE, Melnick RL, Solleveld HA, Hasemann JK, Power M, Miller RA (1985) Multiple organ carcinogenicity of 1,3-butadiene in B6C3F1 mice after 60 weeks of inhalation exposure. Science 277: 548–549CrossRefGoogle Scholar
  4. Kreiling R, Laib RJ, Filser JG, Bolt HM (1987) Inhalation pharmacokinetics of 1,2-epoxybutene-3 reveal species differences between rats and mice sensitive to butadiene induced carcinogenesis. Arch Toxicol 61: 7–11PubMedCrossRefGoogle Scholar
  5. Laib RJ, Bolt HM (1977) Alkylation of RNA by vinyl chloride metabolites in vitro and in vivo: formation of 1, N6-ethenodenosine. Toxicology 8: 185–195PubMedCrossRefGoogle Scholar
  6. Laib RJ, Filser JG, Kreiling R, Vangala RR, Bolt HM (1988) Inhalation pharmacokinetics of 1,3-butadiene and l,2-epoxybutene-3 in rats and mice. Envim. Health Perspect, in pressGoogle Scholar
  7. Laib RJ, Filser JG, Kreiling R, Vangala RR, Bolt HM (1988) Inhalation pharmacokinetics of 1,3-butadiene and l,2-epoxybutene-3 in rats and mice. Envim. Health Perspect, in press Malvoisin E and Roberfroid M (1982) Hepatic microsomal metabolism of 1,3-butadiene. Xenobiotica 12: 137–144PubMedCrossRefGoogle Scholar
  8. Sterzel W, Bedford P, Eisenbrand G (1984) Automated determination of DNA using the fluorochrome Hoechst 33258. Anal Biochem 147: 462–467CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • B. Jelitto
    • 1
  • R. R. Vangala
    • 1
  • R. J. Laib
    • 1
  1. 1.Abteilung für Toxikologie und ArbeitsmedizinInstitut für Arbeitsphysiologie an der Universität DortmundDortmundGermany

Personalised recommendations