title: Evaluation in vitro of several pyrrolizidine alkaloid carcinogens: observations on the essential pyrrolic nucleus.
abstract: Six compounds related to pyrrolizidine alkaloids have been subjected to an in vitro mammalian cell transformation test. Two hepatocarcinogenic alkaloids (retrorsine and monocrotaline) and one synthetic analogue (synthanecine A bis-N-ethylcarbamate) gave positive results while a non-toxic alkaloid (rosmarinine) was negative in the test. Positive results were also given by dehydroretronecine, a secondary pyrrolic alkaloid metabolite, and the closely related synthetic compound 2,3-bishydroxymethyl-1-methylpyrrole. These observations lend support to the hypothesis that a simple alkylating pyrrole is the biologically active chemical agent derived from these alkaloids. The negative transformation response observed for the non-carcinogenic alkaloid rosmarinine establishes that the carcinogenic alkaloids are inducing transformation rather than simply selecting for spontaneous transformants. The mammalian-derived cells used in this study, unlike S. typhimurium, were capable of activating retrorsine in the absence of an auxiliary source of metabolising enzymes (S-9 mix).
authors.affiliation: Imperial Chemical Industries Limited, Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK.
authors.forename: J
authors.initials: J
authors.lastname: Styles
authors.forename: J
authors.initials: J
authors.lastname: Ashby
authors.forename: A R
authors.initials: AR
authors.lastname: Mattocks
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity; D000975:Antioxidants / Q000494:pharmacology; D002273:Carcinogens / Q000633:toxicity*; D002467:Cell Nucleus / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D002934:Cinnamates / Q000494:pharmacology; D053630:Depsides / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects; D016686:Monocrotaline / Q000633:toxicity; D011763:Pyrrolizidine Alkaloids / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000097123:Rosmarinic Acid
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D002273:Carcinogens; D002934:Cinnamates; D053630:Depsides; D016686:Monocrotaline; D011763:Pyrrolizidine Alkaloids; D000097123:Rosmarinic Acid; C003300:retrorsine