Pyrrolizidine alkaloids--genotoxicity, metabolism enzymes, metabolic activation, and mechanisms.
Pyrrolizidine alkaloid-containing plants are widely distributed in the world and are probably the most common poisonous plants affecting livestock, wildlife, and humans. Because of their abundance and potent toxicities, the mechanisms by which pyrrolizidine alkaloids induce genotoxicities, particularly carcinogenicity, were extensively studied for several decades but not exclusively elucidated until recently. To date, the pyrrolizidine alkaloid-induced genotoxicities were revealed to be elicited by the hepatic metabolism of these naturally occurring toxins. In this review, we present updated information on the metabolism, metabolizing enzymes, and the mechanisms by which pyrrolizidine alkaloids exert genotoxicity and tumorigenicity.
Fu
Peter P
PP
National Center for Toxicological Research, Jefferson, Arkansas 72079, USA. pfu@nctr.fda.gov
Xia
Qingsu
Q
Lin
Ge
G
Chou
Ming W
MW
D000818:Animals; D015197:Carcinogenicity Tests; D002986:Clinical Trials as Topic; D018736:DNA Adducts / Q000096:biosynthesis; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology; D008297:Male; D009152:Mutagenicity Tests; D009369:Neoplasms / Q000139:chemically induced* / Q000235:genetics; D010939:Plant Poisoning / Q000378:metabolism*; D011763:Pyrrolizidine Alkaloids / Q000378:metabolism* / Q000633:toxicity; D012737:Sex Factors; D013045:Species Specificity
D018736:DNA Adducts; D011763:Pyrrolizidine Alkaloids