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Genotoxic Pyrrolizidine Alkaloids — Mechanisms Leading to DNA Adduct Formation and Tumorigenicity
National Center for Toxicological Research, Jefferson, AR 72079, USA
Department of Pharmacology, The Chinese University of Hong Kong, Shatin, Hong Kong
* Author to whom correspondence should be addressed.
Received: 7 June 2002; Accepted: 15 August 2002 / Published: 30 September 2002
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.
Keywords: Pyrrolizidine alkaloids; tumorigenicity; riddelliine; DNA adducts; genotoxic mechanism
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Fu, P.P.; Xia, Q.; Lin, G.; Chou, M.W. Genotoxic Pyrrolizidine Alkaloids — Mechanisms Leading to DNA Adduct Formation and Tumorigenicity. Int. J. Mol. Sci. 2002, 3, 948-964.
Fu PP, Xia Q, Lin G, Chou MW. Genotoxic Pyrrolizidine Alkaloids — Mechanisms Leading to DNA Adduct Formation and Tumorigenicity. International Journal of Molecular Sciences. 2002; 3(9):948-964.
Fu, Peter P.; Xia, Qingsu; Lin, Ge; Chou, Ming W. 2002. "Genotoxic Pyrrolizidine Alkaloids — Mechanisms Leading to DNA Adduct Formation and Tumorigenicity." Int. J. Mol. Sci. 3, no. 9: 948-964.