The views presented in this article do not necessarily reflect those of the US Food and Drug Administration.
Article first published online: 28 JAN 2010
Copyright © 2010 John Wiley & Sons, Ltd.
Journal of Applied Toxicology
Volume 30, Issue 3, pages 183–196, April 2010
How to Cite
Chen, T., Mei, N. and Fu, P. P. (2010), Genotoxicity of pyrrolizidine alkaloids. J. Appl. Toxicol., 30: 183–196. doi: 10.1002/jat.1504
This article is a US Government work and is in the public damain in the USA.
- Issue published online: 22 APR 2010
- Article first published online: 28 JAN 2010
- Manuscript Accepted: 16 NOV 2009
- Manuscript Received: 7 OCT 2009
- pyrrolizidine alkaloid;
- DNA damage;
- mutational signature
Pyrrolizidine alkaloids (PAs) are common constituents of many plant species around the world. PA-containing plants are probably the most common poisonous plants affecting livestock and wildlife. They can inflict harm to humans through contaminated food sources, herbal medicines and dietary supplements. Half of the identified PAs are genotoxic and many of them are tumorigenic. The mutagenicity of PAs has been extensively studied in different biological systems. Upon metabolic activation, PAs produce DNA adducts, DNA cross-linking, DNA breaks, sister chromatid exchange, micronuclei, chromosomal aberrations, gene mutations and chromosome mutations in vivo and in vitro. PAs induced mutations in the cII gene of rat liver and in the p53 and K-ras genes of mouse liver tumors. It has been suggested that all PAs produce a set of (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine-derived DNA adducts and similar types of gene mutations. The signature types of mutations are G : C → T : A transversion and tandem base substitutions. Overall, PAs are mutagenic in vivo and in vitro and their mutagenicity appears to be responsible for the carcinogenesis of PAs. Published in 2010 by John Wiley & Sons, Ltd.