Abstract
Pyrrolizidine alkaloids (PAs) are common constituents of many plant species around the world. PAโcontaining 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 crossโlinking, 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 p__53 and Kโras genes of mouse liver tumors. It has been suggested that all PAs produce a set of (ยฑ)โ6,7โdihydroโ7โhydroxyโ1โhydroxymethylโ5__Hโpyrrolizineโderived DNA adducts and similar types of gene mutations. The signature types of mutations are Gโ:โC โ Tโ:โA 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.