Genotoxic Pyrrolizidine Alkaloids — Mechanisms Leading to DNA Adduct Formation and Tumorigenicity

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Fu, Peter P. ; Xia, Qingsu ; Lin, Ge ; Chou, Ming W. (2002)
  • Publisher: Molecular Diversity Preservation International
  • Journal: International Journal of Molecular Sciences (issn: 1422-0067)
  • Related identifiers: doi: 10.3390/i3090948
  • Subject: Chemistry | Pyrrolizidine alkaloids | QD1-999 | genotoxic mechanism | riddelliine | QH301-705.5 | tumorigenicity | DNA adducts | Biology (General)
    mesheuropmc: endocrine system | complex mixtures | heterocyclic compounds | organic chemicals

Abstract: Plants that contain pyrrolizidine alkaloids are widely distributed in the world. Although pyrrolizidine alkaloids have been shown to be genotoxic and tumorigenic in experimental animals, the mechanisms of actions have not been fully understood. The results of our recent mechanistic studies suggest that pyrrolizidine alkaloids induce tumors via a genotoxic mechanism mediated by 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5Hpyrrolizine (DHP)-derived DNA adduct formation. This mechanism may be general to most carcinogenic pyrrolizidine alkaloids, including the retronecine-, heliotridine-, and otonecinetype pyrrolizidine alkaloids. It is hypothesized that these DHP-derived DNA adducts are potential biomarkers of pyrrolizidine alkaloid tumorigenicity. The mechanisms that involve the formation of DNA cross-linking and endogenous DNA adducts are also discussed.
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