The sesquiterpene lactone hymenoxon acts as a bifunctional alkylating agent

Victor L. Sylvia, Hyeong L. Kim, James O. Normanand, David L. Busbee

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Hymenoxon, a toxic sesquiterpene lactone found in bitterweed, bound deoxyguanosine in a cell free system and formed adducts with guanine residues in cellular DNA. The reactive dialdehyde form of hymenoxon formed stable Schiff base products with deoxyguanosine which were separable from unreacted hymenoxon and deoxynucleosides by reverse phase high pressure liquid chromatography. Hymenoxon adducts which eluted as a single impure peak from the octadecylsilane column separated on amino and diphenyl-bonded phases with 10% methanol. Tritiated nucleoside adducts were isolated and purified from CFW mouse sarcoma cells treated with hymenoxon. Proton nuclear magnetic resonance spectra of purified hymenoxon-deoxyguanosine adducts revealed a loss of signals for hydroxyl groups in the bishemiacetal of hymenoxon. 13C-nuclear magnetic resonance spectra revealed that the major adduct has 35 carbon atoms, indicating an interaction of at least two guanine residues per hymenoxon molecule and suggesting that hymenoxon may cross-link DNA. Sedimentation analysis of treated DNA further showed that DNA cross-linking by hymenoxon (30 μg/ml) was equivalent to that of a known cross-linking agent, mitomycin C (7.5 μg/ml). Hymenoxon was more cytotoxic to DNA cross-link repair-deficient Chinese hamster ovary cell mutants than to repair proficient strains. These data combine to indicate that hymenoxon acts as a bifunctional alkylating agent which cross-links DNA in mammalian cells.

Original languageEnglish (US)
Pages (from-to)39-49
Number of pages11
JournalCell Biology and Toxicology
Volume3
Issue number1
DOIs
StatePublished - Mar 1987
Externally publishedYes

Keywords

  • bitterweed
  • DNA adduct
  • DNA cross-linking
  • hymenoxon
  • sesquiterpene lactone

ASJC Scopus subject areas

  • Toxicology
  • Cell Biology
  • Health, Toxicology and Mutagenesis

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