title: Metabolism, genotoxicity, and carcinogenicity of comfrey.
abstract: Comfrey has been consumed by humans as a vegetable and a tea and used as an herbal medicine for more than 2000 years. Comfrey, however, produces hepatotoxicity in livestock and humans and carcinogenicity in experimental animals. Comfrey contains as many as 14 pyrrolizidine alkaloids (PA), including 7-acetylintermedine, 7-acetyllycopsamine, echimidine, intermedine, lasiocarpine, lycopsamine, myoscorpine, symlandine, symphytine, and symviridine. The mechanisms underlying comfrey-induced genotoxicity and carcinogenicity are still not fully understood. The available evidence suggests that the active metabolites of PA in comfrey interact with DNA in liver endothelial cells and hepatocytes, resulting in DNA damage, mutation induction, and cancer development. Genotoxicities attributed to comfrey and riddelliine (a representative genotoxic PA and a proven rodent mutagen and carcinogen) are discussed in this review. Both of these compounds induced similar profiles of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts and similar mutation spectra. Further, the two agents share common mechanisms of drug metabolism and carcinogenesis. Overall, comfrey is mutagenic in liver, and PA contained in comfrey appear to be responsible for comfrey-induced toxicity and tumor induction.
authors.affiliation: Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079, USA. nan.mei@fda.hhs.gov
authors.forename: Nan
authors.initials: N
authors.lastname: Mei
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.forename: Peter P
authors.initials: PP
authors.lastname: Fu
authors.forename: James C
authors.initials: JC
authors.lastname: Fuscoe
authors.forename: Yang
authors.initials: Y
authors.lastname: Luan
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D020844:Comfrey / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009153:Mutagens / Q000633:toxicity; D028321:Plant Preparations / Q000633:toxicity; D011763:Pyrrolizidine Alkaloids / Q000032:analysis / Q000633:toxicity; D051381:Rats
chemical_list: D002273:Carcinogens; D009153:Mutagens; D028321:Plant Preparations; D011763:Pyrrolizidine Alkaloids